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 CADD and AlphaMissense predictions. Also enable allele frequencies from gnomAD genomes, and Phenotypes. 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 in gnomAD genomes?
Go to the Ensembl homepage and click on the EnsVEP* app on the top of the page. Begin by clicking “Choose a Genome” and select Human GRCh38.p14. Then click “+” in the Variants row to add variants and paste your variants there in this format:
#CHROM POS ID REF ALT QUAL FILTER INFO
7 117530985 var1 G A . . .
7 117531038 var2 T C . . .
7 117531068 var3 T C . . .
Note: Variation data input must be in VCF format. See more details about using VEP in the documentation page. Click Run. When your job is has finished running the Results button will becom available. click View Results.
You will get a table with the predicted 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. AlphaMissense scores are available for missense SNPs only. For two of the entered positions, the variations have been predicted to have missense consequences of various pathogenicity (var2 - coordinate 117531038 and -var3 117531068), both affecting CFTR. All the three variants have been identified and have frequencies in gnomAD genomes.
