Determining the Effect of Genomic Variants Using the Ensembl Variant Effect Predictor
The effect of newly discovered genomic variants on known transcripts is indispensable in prioritising and categorising such variants. The Ensembl Variant Effect Predictor (VEP) functionally annotates variants in all Ensembl and Ensembl Genomes supported species. Annotation includes, amongst others, the effect on Ensembl annotated transcripts, the existence of already known co-located variants and, for non-synonymous variants in human, the functional effect as predicted by the SIFT and PolyPhen tools. The VEP is available as a web-based tool, that can be used for sets of up to 750 variants, as well as a downloadable script that can be used for larger datasets.
Both the web-based tool and the script are available on http://www.ensembl.org/tools.html. To be able to use the script the Ensembl Core and Variation API should be installed first (see http://www.ensembl.org/info/docs/api/api_installation.html).
Accepted data formats
The VEP accepts substitutions, insertions and deletions as input. Input can be provided in VCF or Pileup format, or in a simple tab-separated format, that consists of five columns, i.e. chromosome, start, end, alleles and strand. In the tab-separated format the start coordinate of an insertion should be equal to the end coordinate + 1.
– Go to http://www.ensembl.org.
– Click on [Tools] in the menubar.
– Access the web-based version of the VEP.
– Select ‘Species: human’.
– Type ‘My variants’ in the ‘Name for this upload’ field.
– Paste the following data into the ‘Paste file’ text box:
7 117171039 117171039 G/A +
7 117171092 117171092 T/C +
7 117171122 117171122 T/C +
Note that additional options can be selected from the ‘Options’ and ‘Non-synonymous SNP predictions (human only)’ sections, if desired.
– Click [Next>].
– Click on ‘HTML’.
This will give the following result:
Note that the values in the Location, Gene, Transcript and Co-located Variation columns are all hyperlinked. Clicking on a location for example will show the genomic region of the uploaded variant on the ‘Region in detail’ page in the Ensembl browser (uploaded variants are shown in the ‘My variants’ track):
Any questions with regard to the VEP can be directed to firstname.lastname@example.org.