Demo: Introduction to Ensembl

Ensembl

Homepage

The front page of Ensembl is found at ensembl.org. It contains lots of information and links to help you navigate Ensembl:

On the right-hand panel you can see the current release number and what has come out in this release. To access old releases, scroll to the bottom of the page and click on View in archive site in the right-hand corner.

Click on the links to go to the archives. Alternatively, you can jump quickly to the correct release by adding e plus the release number in the URL. For example e98.ensembl.org jumps to Ensembl release 98.  
 
 

Available species

Scroll back up to the top of the homepage. You can view all available species by clicking the View full list of all species link underneath the coloured search block.

You can search for your species of interest (either the common or scientific name) using the search bar at the top right-hand corner of the table. Click on the common name of your species of interest to go to the species information page. We’ll click on Human.

 
 
 

Species information

Here you can see links to example features and to download flatfiles. To find out more about the genome assembly and genebuild, click on More information and statistics under the Genome assembly section.

Here you’ll find a detailed description of how to the genome was produced and links to the original source. You will also see details of how the genes were annotated.

The current genome assembly for human is GRCh38. If you want to see the previous assembly, GRCh37, visit our dedicated site grch37.ensembl.org.

 
 
 

Ensembl Genomes

Homepage

Let’s take a look at the Ensembl Genomes homepage at ensemblgenomes.org.

Click on the different taxa to see their homepages. Each one has a different colour-coding, but they are all structured in a similar format to the Ensembl main site.

You can navigate most of the taxa in the same way as you would with Ensembl.  
 
 

Ensembl Bacteria

Ensembl Bacteria has a large number of genomes and has a slightly different method to the other Ensembl sites. Let’s look at it in more detail.

There’s no drop-down species list for bacteria as it would be hard to navigate with the number of species. You can click the View full list of all Ensembl Bacteria species link underneath the coloured search block. Search for your species of interest using the filter in the top right-hand corner of the table.

Alternatively, you can find a species by typing the species name into the Search for a genome search box at the top of the page. A drop-down list will appear with any species matching the name you entered.

For example, to find a sub-strain of Clostridioides difficile start typing in the species name. Due to the auto-complete, you’ll see useful results as soon as you get to Clostridio.

The drop down contains various strains of C. difficile. Let’s choose C. difficile 630. This will take us to another species information page, where we can explore various features.

Unlike the Homo sapiens species information page, there is no prose description of the genome or gene annotation, as these pages were generated automatically.  
 
 

Ensembl Rapid Release

Our newest genomes, such as those coming from the Darwin Tree of Life, are available rapid.ensembl.org with limited annotation.

Go to Ensembl and find the following information:

1. What is the name of the genome assembly for Panda?

2. How long is the Panda genome (in bp)? How many coding genes have been annotated?

What previous assemblies are available for zebrafish?

Go to Ensembl Plants and answer the following questions:

1. How many genomes of the genus Solanum are there in Ensembl Plants?

2. When was the current Solanum lycopersicum genome assembly last revised?

1. Go to Ensembl Metazoa. How many genomes relating to the genus Anopheles are there in Ensembl Metazoa?

2. When was the current Anopheles gambiae genome assembly last revised?

Mycobacterium tuberculosis H37Ra str. ATCC25177 is a clinical strain.

Go to Ensembl Bacteria and find the species M. tuberculosis H37Ra str. ATCC25177. How many coding genes does it have?

Start at the Ensembl front page, ensembl.org. You can search for a region by typing it into a search box, but you have to specify the species.

To bypass the text search, you need to input your region coordinates in the correct format, which is chromosome, colon, start coordinate, dash, end coordinate, with no spaces for example: human 4:122868000-122946000. Type (or copy and paste) these coordinates into either search box.

or

Press Enter or click Go to jump directly to the Region in detail Page.

Click on the button to view page-specific help. The help pages provide text, labelled images and, in some cases, help videos to describe what you can see on the page and how to interact with it.

The Region in detail page is made up of three images, let’s look at each one in detail.

The first image shows the chromosome:

The region we’re looking at is highlighted on the chromosome. You can jump to a different region by dragging out a box in this image. Drag out a box on the chromosome, a pop-up menu will appear.

If you wanted to move to the region, you could click on Jump to region (### bp). If you wanted to highlight it, click on Mark region (###bp). For now, we’ll close the pop-up by clicking on the X on the corner.

The second image shows a 1Mb region around our selected region. This is always 1Mb in human, but the fixed size of this view varies between species. This view allows you to scroll back and forth along the chromosome.

You can also drag out and jump to or mark a region.

Click on the X to close the pop-up menu.

Click on the Drag/Select button to change the action of your mouse click. Now you can scroll along the chromosome by clicking and dragging within the image. As you do this you’ll see the image below grey out and two blue buttons appear. Clicking on Update this image would jump the lower image to the region central to the scrollable image. We want to go back to where we started, so we’ll click on Reset scrollable image.

The third image is a detailed, configurable view of the region.

Here you can see various tracks, which is what we call a data type that you can plot against the genome. Some tracks, such as the transcripts, can be on the forward or reverse strand. Forward stranded features are shown above the blue contig track that runs across the middle of the image, with reverse stranded features below the contig. Other tracks, such as variants, regulatory features or conserved regions, refer to both strands of the genome, and these are shown by default at the very top or very bottom of the view.

You can use click and drag to either navigate around the region or highlight regions of interest, Click on the Drag/Select option at the top or bottom right to switch mouse action. On Drag, you can click and drag left or right to move along the genome, the page will reload when you drop the mouse button. On Select you can drag out a box to highlight or zoom in on a region of interest.

With the tool set to Select, drag out a box around an exon and choose Mark region.

The highlight will remain in place if you zoom in and out or move around the region. This allows you to keep track of regions or features of interest.

We can edit what we see on this page by clicking on the blue Configure this page menu at the left.

This will open a menu that allows you to change the image.

There are thousands of possible tracks that you can add. When you launch the view, you will see all the tracks that are currently turned on with their names on the left and an info icon on the right, which you can click on to expand the description of the track. Turn them on or off, or change the track style by clicking on the box next to the name. More details about the different track styles are in this FAQ: http://www.ensembl.org/Help/Faq?id=335.

You can find more tracks to add by either exploring the categories on the left, or using the Find a track option at the top left. Type in a word or phrase to find tracks with it in the track name or description.

Let’s add some tracks to this image. Add:

• Proteins (mammal) from UniProt – Labels
• 1000 Genomes - All - short variants (SNPs and indels) – Normal

Now click on the tick in the top left hand to save and close the menu. Alternatively, click anywhere outside of the menu. We can now see the tracks in the image. The proteins track is stranded, so you will see two tracks, one above and one below the contig, representing the proteins mapped to the forward and reverse strands respectively. The variants track is not stranded, so is found near the bottom of the image.

If the track is not giving you can information you need, you can easily change the way the tracks appear by hovering over the track name then the cog wheel to open a menu. To make it easier to compare information between tracks, such as spotting overlaps, you can move tracks around by clicking and dragging on the bar to the left of the track name.

Now that you’ve got the view how you want it, you might like to show something you’ve found to a colleague or collaborator. Click on the Share this page button to generate a link. Email the link to someone else, so that they can see the same view as you, including all the tracks you’ve added. These links contain the Ensembl release number, so if a new release or even assembly comes out, your link will just take you to the archive site for the release it was made on.

To return this to the default view, go to Configure this page and select Reset configuration at the bottom of the menu.

Go to Ensembl.

1. Go to the region from 32,264,000 to 32,492,000 bp on human chromosome 13. On which cytogenetic band is this region located? How many contigs make up this portion of the assembly (contigs are contiguous stretches of DNA sequence that have been assembled solely based on direct sequencing information)?

2. Zoom in on the BRCA2 gene.

3. Configure this page to turn on the LTR (repeat) track in this view. What tool was used to annotate the LTRs according to the track information? How many LTRs can you see within the BRCA2 gene? Do any overlap exons?

4. Create a Share link for this display. Email it to your neighbour. Open the link they sent you and compare. If there are differences, can you work out why?

5. Export the genomic sequence of the region you are looking at in FASTA format.

6. Turn off all tracks you added to the Region in detail page.

You want to do some CRISPR manipulation of the human SMC3 gene. You’re looking for a CRISPR editing site within the locus 10:110578600-110578700.

(a) Go to the locus above and turn on the CRISPR track. How many CRISPR sites can you see in this locus?

(b) Do any of the CRISPR sites overlap any phenotype causing variants? What are the identifiers of these sites and variants?

(c) Mark the region of the negative strand CRISPR site that overlaps these variants, then zoom out to see the whole SMC3 gene. What exon number is your CRISPR site found in the SMC3-201 transcript?

You can find out lots of information about Ensembl genes and transcripts using the browser. If you’re already looking at a region view, you can click on any transcript and a pop-up menu will appear, allowing you to jump directly to that gene or transcript.

Alternatively, you can find a gene by searching for it. You can search for gene names or identifiers, and also phenotypes or functions that might be associated with the genes.

We’re going to look at the human UQCRQ gene. From ensembl.org, type UQCRQ into the search bar and click the Go button. You will get a list of hits with the human gene at the top.

Where you search for something without specifying the species, or where the ID is not restricted to a single species, the most popular species will appear first, in this case, human, mouse and zebrafish appear first. You can restrict your query to species or features of interest using the options on the left.

The gene tab

Click on the gene name or Ensembl ID. The Gene tab should open:

This page summarises the gene, including its location, name and equivalents in other databases. At the bottom of the page, a graphic shows a region view with the transcripts. We can see exons shown as blocks with introns as lines linking them together. Coding exons are filled, whereas non-coding exons are empty. We can also see the overlapping and neighbouring genes and other genomic features.

There are different tabs for different types of features, such as genes, transcripts or variants. These appear side-by-side across the blue bar, allowing you to jump back and forth between features of interest. Each tab has its own navigation column down the left hand side of the page, listing all the things you can see for this feature.

Let’s walk through this menu for the gene tab. How can we view the genomic sequence? Click Sequence at the left of the page.

The sequence is shown in FASTA format. The FASTA header contains the genome assembly, chromosome, coordinates and strand (1 or -1) – this gene is on the positive strand.

Exons are highlighted within the genomic sequence, both exons of our gene of interest and any neighbouring or overlapping gene. By default, 600 bases are shown up and downstream of the gene. We can make changes to how this sequence appears with the blue Configure this page button found at the left. This allows us to change the flanking regions, add variants, add line numbering and more. Click on it now.

Once you have selected changes (in this example, Show variants, 1000 Genomes variants and Line numbering) click at the top right.

You can download this sequence by clicking in the Download sequence button above the sequence:

This will open a dialogue box that allows you to pick between plain FASTA sequence, or sequence in RTF, which includes all the coloured annotations and can be opened in a word processor. If you want run a sequence analysis tool, download as FASTA sequence, whereas if you want to analyse the sequence visually, RTF is best for this. This button is available for all sequence views.

To find out what the protein does, have a look at GO terms from the Gene Ontology consortium. There are three pages of GO terms, representing the three divisions in GO: Biological process (what the protein does), Cellular component (where the protein is) and Molecular function (how it does it). Click on GO: Biological process to see an example of the GO pages.

Here you can see the functions that have been associated with the gene. There are three-letter codes that indicate how the association was made, as well as links to the specific transcript they are linked to.

We also have links out to other databases which have information about our genes and may focus on other topics that we don’t cover, like Gene Expression Atlas or OMIM. Go up the left-hand menu to External references:

Demo: The transcript tab

We’re now going to explore the different transcripts of UQCRQ. Click on Show transcript table at the top.

Here we can see a list of all the transcripts of UQCRQ with their identifiers, lengths, biotypes and flags to help you decide which ones to look at.

If we were to only choose one transcript to analyse, we would choose UQCRQ-203 because it is the MANE Select and Ensembl Canonical. This means it is both 100% identical to the RefSeq transcript NM_014402.5 and both Ensembl and NCBI agree that it is the most biologically important transcript.

Click on the ID, ENST00000378670.8.

You are now in the Transcript tab for UQCRQ-203. We can still see the gene tab so we can easily jump back. The left hand navigation column provides several options for the transcript UQCRQ-203 - many of these are similar to the options you see in the gene tab, but not all of them. If you can’t find the thing you’re looking for, often the solution is to switch tabs.

Click on the Exons link. This page is useful for designing RT-PCR primers because you can see the sequences of the different exons and their lengths.

You may want to change the display (for example, to show more flanking sequence, or to show full introns). In order to do so click on Configure this page and change the display options accordingly.

Now click on the cDNA link to see the spliced transcript sequence with the amino acid sequence. This page is useful for mapping between the RNA and protein sequences, particularly genetic variants.

UnTranslated Regions (UTRs) are highlighted in dark yellow, codons are highlighted in light yellow, and exon sequence is shown in black or blue letters to show exon divides. Sequence variants are represented by highlighted nucleotides and clickable IUPAC codes are above the sequence.

Next, follow the General identifiers link at the left. Just like the External References page in the gene tab, this page shows links out to other databases such as RefSeq, UniProtKB, PDBe and others, this time linked to the transcript or protein product, rather than the gene.

If you’re interested in protein domains, you could click on Protein summary to view domains from Pfam, PROSITE, Superfamily, InterPro, and more. These are all plotted against the transcript sequence, with the exons shown in alternating shades of purple at the top of the page. Alternatively, you can go to Domains & features to see a table of the same information.

You can also see the structure of the protein from the PDB by clicking on PDB 3D Protein model.

This uses LiteMol to show a 3D protein. You can use all the normal controls that you would use with LiteMol, plus plot Ensembl features like Exons and variants onto the structure using the options on the right. We allow you to see the top ten PDB models for this protein, based on coverage and quality scores, you can choose which at the top of the viewer.

1. In Ensembl, find the human MYH9 (myosin, heavy chain 9, non-muscle) gene and open the Gene tab.
   • On which chromosome and which strand of the genome is this gene located?
   • How many transcripts (splice variants) are there and how many are protein coding?
   • What is the longest protein-coding transcript, and how long is the protein it encodes?
   • Which transcript would you take forward for further study?

2. Click on Phenotypes at the left side of the page. Are there any diseases associated with this gene, according to Mendelian Inheritance in Man (MIM)?

3. What are some functions of MYH9 according to the Gene Ontology (GO) consortium? Have a look at the GO: Biological process pages for this gene.

4. In the transcript table, click on the transcript ID for MYH9-201, and go to the Transcript tab.
   • How many exons does it have?
   • Are any of the exons completely or partially untranslated?
   • Is there an associated sequence in UniProtKB/Swiss-Prot? Have a look at the General identifiers for this transcript.
5. Are there microarray (oligo) probes that can be used to monitor ENST00000216181 expression?

Phenylketonuria is a genetic disorder caused by an inability to metabolise phenylalanine in any body tissue. This results in an accumulation of phenylalanine causing seizures and intellectual disability.

(a) Search for phenylketonuria from the Ensembl homepage and narrow down your search to only genes. What gene is associated with this disorder?

(b) How many protein coding transcripts does this gene have? View all of these in the transcript comparison view.

(c) What is the MIM gene identifier for this gene?

(d) Go to the MANE Select transcript and look at its 3D structure. In the model 2pah, how many protein molecules can you see?

In any of the sequence views shown in the Gene and Transcript tabs, you can view variants on the sequence. You can do this by clicking on Configure this page from any of these views.

Let’s take a look at the Gene sequence view for HBB in human. Search for HBB and go to the Sequence view.

If you can’t see variants marked on this view, click on Configure this page and select Show variants: Yes and show links. You may also wish to add a filter to the variants to allow them to load more quickly, we’ll add Filter variants by evidence status: 1000Genomes.

Find out more about a variant by clicking on it.

You can add variants to all other sequence views in the same way.

You can go to the Variation tab by clicking on the variant ID. For now, we’ll explore more ways of finding variants.

To view all the sequence variants in table form, click the Variant table link at the left of the gene tab.

You can filter the table to only show the variants you’re interested in. For example, click on Consequences: All, then select the variant consequences you’re interested in. For display purposes, the table above has already been filtered to only show missense variants.

You can also filter by the different pathogenicity scores and MAF, or click on Filter other columns for filtering by other columns such as Evidence or Class.

The table contains lots of information about the variants. You can click on the IDs here to go to the Variation tab too.

You can also see the phenotypes associated with a gene. Click on Phenotype in the left hand menu.

Open the transcript table and go to HBB-201 ENST00000335295, then click on Haplotypes in the left hand menu.

The Haplotypes view in the transcript tab shows you the actual protein and CDS sequences in 1000 Genomes individuals. This is possible because the 1000 Genomes study has phased genotypes, so we know which alleles occur on which of the chromosome pairs. The table lists all the versions of the protein that occur along with their frequencies, including the reference sequence and sequences with one or more alternative alleles.

Click on one of the haplotypes, we’ll go for 18K>*,​19del{130}, to find out more about it. Here you will see the frequency in the 1000 Genomes subpopulations, the sequence and the 1000 Genomes individuals where this protein is found.

Let’s have a look at variants in the Location tab. Click on the Location tab in the top bar.

Configure this page and open Variation from the left-hand menu.

There are various options for turning on variants. You can turn on variants by source, by frequency, presence of a phenotype or by individual genome they were isolated from. You can also turn on genotyping chips.

Let’s have a look at a specific variant. If we zoomed in we could see the variant rs334 in this region, however it’s easier to find if we put rs334 into the search box. Click through to open the Variation tab.

The icons show you what information is available for this variant. Click on Genes and regulation, or follow the link on the left.

This page illustrates the genes the variant falls within and the consequences on those genes, including pathogenicity predictors. It also shows data from GTEx on genes that have increased/decreased expression in individuals with this variant, in different tissues. Finally, regulatory features and motifs that the variant falls within are shown.

We can also see the variant in the protein structure by clicking on 3D Protein model.

This is a LiteMol viewer, where you can rotate and zoom in on the structure. The variant location is highlighted, so you can see where it lands within the structure.

Let’s look at population genetics. Click on Population genetics in the left-hand menu.

The population allele frequencies are shown by study, including 1000 Genomes and gnomAD. Where genotype frequencies are available, these are shown in the tables.

There are big differences in allele frequencies between populations. Let’s have a look at the phenotypes associated with this variant to see if they are known to be specific to certain human populations. Click on Phenotype Data in the left-hand menu.

This variant is associated with various phenotypes, including sickle cell and malaria resistance. These phenotype associations come from sources including the GWAS catalog, ClinVar, Orphanet and OMIM. Where available, there are links to the original paper that made the association, the allele that is associated with the phenotype and p-values and other statistics.

The SNP rs1738074 in the 5’ UTR of the human TAGAP gene has been identified as a genetic risk factor for a few diseases. Use Ensembl to answer the following questions:

1. In which transcripts is this SNP found?

2. What is the least frequent genotype for this SNP in the Yoruba (YRI) population from the 1000 Genomes phase 3?

3. What is the ancestral allele? Is it conserved in the 91 eutherian mammals EPO-Extended?

4. With which diseases is this SNP associated? Are there any known risk (or associated) alleles?

The missense variation rs1801133 in the human MTHFR gene has been linked to elevated levels of homocysteine, an amino acid whose plasma concentration seems to be associated with the risk of cardiovascular diseases, neural tube defects, and loss of cognitive function.

1. Find the page with information for rs1801133.

2. Is rs1801133 a missense variant in all transcripts of the MTHFR gene? What is the amino acid change?

3. Why are the alleles for this variation in Ensembl given as G/A and not as C/T, as in the literature?

4. What is the major allele of rs1801133 in different populations?

5. In which paper(s) is the association between rs1801133 and homocysteine levels described?

6. According to the data imported from dbSNP, the ancestral allele for rs1801133 is G. Ancestral alleles in dbSNP are based on a comparison between human and chimp. Does the sequence at this same position in other primates confirm that the ancestral allele is G?

Variable number tandem repeats (VNTRs) show high variation in the number of repeats in the population and are commonly used in forensics (DNA fingerprinting) and to study genetic diversity. (a) Go to the region from 3074666 to 3075100 bp on human chromosome 4. Which gene does it overlap? Which exon of this gene falls in this region?

(b) Configure this page to turn on Repeats (low), Simple repeats (Repeats (low)) and Tandem repeats (TRF) tracks in this view. Can you see any repeats in this exon? What tools were used to annotate the repeats according to the track information?

(c) Zoom in on the (CAG)n to see its sequence. How many CAG repeats can you see in the human reference assembly? Does this track overlap any phenotype-associated variants? What is the identifier of this variant?

(d) Go to the variant tab of the phenotype-associated variant. What is the consequence ontology of this variant? Does the reference allele match the number of repeats you have just counted? What is the shortest and longest allele?

We have identified five variants on human chromosome nine, C-> A at 128203516, an A deletion at 128328461, C->A at 128322349, C->G at 128323079 and G->A at 128322917.

We will use the Ensembl VEP to determine:

• Have my variants already been annotated in Ensembl?
• What genes are affected by my variants?
• Do any of my variants affect gene regulation?

Go to the front page of Ensembl and click on the Variant Effect Predictor.

This page contains information about the VEP, including links to download the script version of the tool. Click on Launch VEP to open the input form:

The data is in VCF format:
chromosome coordinate id reference alternative

Put the following into the Paste data box:
9 128328460 var1 TA T
9 128322349 var2 C A
9 128323079 var3 C G
9 128322917 var4 G A
9 128203516 var5 C A

The VEP will automatically detect that the data is in VCF.

There are further options that you can choose for your output. These are categorised as Identifiers, Variants and frequency data, Additional annotations, Predictions, Filtering options and Advanced options. Let’s open all the menus and take a look.

Hover over the options to see definitions.

We’re going to select some options:

• HGVS, annotation of variants in terms of the transcripts and proteins they affect, commonly-used by the clinical community
• Phenotypes
• Protein domains

When you’ve selected everything you need, scroll right to the bottom and click Run.

The display will show you the status of your job. It will say Queued, then automatically switch to Done when the job is done, you do not need to refresh the page. You can edit or discard your job at this time. If you have submitted multiple jobs, they will all appear here.

Click View results once your job is done.

In your results you will see a graphical summary of your data, as well as a table of your results.

The results table is enormous and detailed, so we’re going to go through the it by section. The first column is Uploaded variant. If your input data contains IDs, like ours does, the ID is listed here. If your input data is only loci, this column will contain the locus and alleles of the variant. You’ll notice that the variants are not neccessarily in the order they were in in your input. You’ll also see that there are multiple lines in the table for each variant, with each line representing one transcript or other feature the variant affects.

You can mouse over any column name to get a definition of what is shown.

The next few columns give the information about the feature the variant affects, including the consequence. Where the feature is a transcript, you will see the gene symbol and stable ID and the transcript stable ID and biotype. Where the feature is a regulatory feature, you will get the stable ID and type. For a transcription factor binding motif (labelled as a MotifFeature) you will see just the ID. Most of the IDs are links to take you to the gene, transcript or regulatory feature homepage.

This is followed by details on the effects on transcripts, including the position of the variant in terms of the exon number, cDNA, CDS and protein, the amino acid and codon change, transcript flags, such as MANE, on the transcript, which can be used to choose a single transcript for variant reporting, and pathogenicity scores. The pathogenicity scores are shown as numbers with coloured highlights to indicate the prediction, and you can mouse-over the scores to get the prediction in words. Two options that we selected in the input form are the HGVS notation, which is shown to the left of the image below and can be used for reporting, and the Domains to the right. The Domains list the proteins domains found, and where there is available, provide a link to the 3D protein model which will launch a LiteMol viewer, highlighting the variant position.

Where the variant is known, the ID of the existing variant is listed, with a link out to the variant homepage. In this example, only rsIDs from dbSNP are shown, but sometimes you will see IDs from other sources such as COSMIC. The VEP also looks up the variant in the Ensembl database and pulls back the allele frequency (AF in the table), which will give you the 1000 Genomes Global Allele Frequency. In our query, we have not selected allele frequencies from the continental 1000 Genomes populations or from gnomAD, but these could also be shown here. We can also see ClinVar clinical significance and the phenotypes associated with known variants or with the genes affected by the variants, with the variant ID listed for variant associations and the gene ID listed for gene associations, along with the source of the association.

For variants that affect transcription factor binding motifs, there are columns that show the effect on motifs (you may need to click on Show/hide columns at the top left of the table to display these). Here you can see the position of the variant in the motif, if the change increases or decreases the binding affinity of the motif and the transcription factors that bind the motif.

Above the table is the Filter option, which allows you to filter by any column in the table. You can select a column from the drop-down, then a logic option from the next drop-down, then type in your filter to the following box. We’ll try a filter of Consequence, followed by is then missense_variant, which will give us only variants that change the amino acid sequence of the protein. You’ll notice that as you type missense_variant, the VEP will make suggestions for an autocomplete.

You can export your VEP results in various formats, including VCF. When you export as VCF, you’ll get all the VEP annotation listed under CSQ in the INFO column. After filtering your data, you’ll see that you have the option to export only the filtered data. You can also drop all the genes you’ve found into the Gene BioMart, or all the known variants into the Variation BioMart to export further information about them.

Resequencing of the genomic region of the human CFTR (cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7) gene (ENSG00000001626) has revealed the following variants. The alleles defined in the forward strand:

• G/A at 7: 117,530,985
• T/C at 7: 117,531,038
• T/C at 7: 117,531,068

Use the VEP tool in Ensembl and choose the options to see SIFT and PolyPhen predictions. Do these variants result in a change in the proteins encoded by any of the Ensembl genes? Which gene? Have the variants already been found?

7	117530985	117530985	G/A
7	117531038	117531038	T/C  
7	117531068	117531068	T/C

We have details of a genomic deletion in a breast cancer sample in VCF format:

13 32307062 sv1 . <DEL> . . SVTYPE=DEL;END=32908738

Use VEP in Ensembl to find out the following information:

1.  How many genes have been affected?

2.  Does the structural variant (SV) cause deletion of any complete transcripts?

3.  Map your variant in the Ensembl browser on the Region in detail view.