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ASHG: Using the new Ensembl genome browser and Variant Effect Predictor (VEP) to analyse and interpret genomic variation data
Course Details
- Lead Trainer
- Aleena Mushtaq
- Event Date
- 2024-11-05
- Location
- Denver
- Description
- This workshop will guide you through the Ensembl/GENCODE and MANE genesets and how to use the new Ensembl genome browser (https://beta.ensembl.org/) and Ensembl VEP to annotate and prioritise genetic variants in the context of the human reference genome assemblies and human pangenomes.
Demos and exercises
Overview of Ensembl Beta
Overview of the current Ensembl genome browser
VEP
Running CFTR variants through VEP
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?
Go to the Ensembl homepage and click on the link Tools at the top of the page. Currently there are nine tools listed in that page. Click on Variant Effect Predictor and enter the three variants as below:
7 117530985 117530985 G/A
7 117531038 117531038 T/C
7 117531068 117531068 T/C
Note: Variation data input can be done in a variety of formats. See more details about the different data formats and their structure in this VEP documentation page. Click Run. When your job is listed as Done, click View Results.
You will get a table with the consequence terms from the Sequence Ontology project (http://www.sequenceontology.org/) (i.e. synonymous, missense, downstream, intronic, 5’ UTR, 3’ UTR, etc) provided by VEP for the listed SNPs. You can also upload the VEP results as a track and view them on Location pages in Ensembl. SIFT and PolyPhen are available for missense SNPs only. For two of the entered positions, the variations have been predicted to have missense consequences of various pathogenicity (coordinate 117531038 and 117531068), both affecting CFTR. All the three variants have been already annotated and are known as rs1800077, rs1800078 and rs35516286 in dbSNP (databases, literature, etc).
VEP analysis of structural variants in human
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.
- Click on VEP at the top of any Ensembl page and open the web interface. Make sure your species is Human. It is good practise to name your VEP jobs something descriptive, such as Patient deletion exercise. Paste the variant in VCF format into the Paste data field and hit Run.
12 different genes are affected by the SV.
- Filter your table by select Consequence is
transcript_ablationat the top of the table and click Add.Yes, there is deletion of complete transcripts of PDS5B, N4BP2L1, BRCA2, RNY1P4, IFIT1P1, ATP8A2P2, N4BP2L2, N4BP2L2-IT2 and one gene without official symbols: ENSG00000212293.
- To view your variant in the browser click on the location link in the results table 13: 32307062-32908738. The link will open the Region in detail view in a new tab. If you have given your data a name it will appear automatically in red. If not, you may need to Configure this page and add it under the Personal data tab in the pop-up menu.
