[ensembl-dev] upstream/downstream changes based on context in vcf?

[Matt Wood]

I've managed to put together a small example with two variants that show
the behavior. I've attached two vcfs.

The variant we're looking at is 22:35998183TTGTGTC>T.

I've found I can reproduce the bug with just the following options:

perl /space1/software/vep/ensembl-vep/vep --dir /vep/cache/ --offline --vcf
--regulatory -i has_downstream.vcf -o has_downstream.vcf.vep

If you run it on no_downstream.vcf we're getting the following output:

22      35998183        .       TTGTGTC T       120     PASS
CSQ=-|TF_binding_site_variant|MODIFIER|||MotifFeature|MA0058.2|||||||||||||-1||||Max:MA0058.2|1|N|,-|intergenic_variant|MODIFIER||||||||||||||||||||||||
GT:VR:RR:DP:GQ  0/1:10:10:20:.

But, if we run it on has_downstream.vcf we get additional downstream
effects for the variant we're looking at:

22      35998183        .       TTGTGTC T       120     PASS
CSQ=-|downstream_gene_variant|MODIFIER|MB|ENSG00000198125|Transcript|ENST00000359787|protein_coding|||||||||||4622|-1||HGNC|6915||||,-|downstream_gene_variant|MODIFIER|MB|ENSG00000198125|Transcript|ENST00000397326|protein_coding|||||||||||4622|-1||HGNC|6915||||,-|downstream_gene_variant|MODIFIER|MB|ENSG00000198125|Transcript|ENST00000397328|protein_coding|||||||||||4622|-1||HGNC|6915||||,-|downstream_gene_variant|MODIFIER|MB|ENSG00000198125|Transcript|ENST00000401702|protein_coding|||||||||||4622|-1||HGNC|6915||||,-|TF_binding_site_variant|MODIFIER|||MotifFeature|MA0058.2|||||||||||||-1||||Max:MA0058.2|1|N|
    GT:VR:RR:DP:GQ  0/1:10:10:20:.

The only difference being the addition of another variant in the vcf.

Our version info:

Versions:
  ensembl              : 89.df47f96
  ensembl-funcgen      : 89.678099a
  ensembl-io           : 89.feefbc2
  ensembl-variation    : 89.af9aae5
  ensembl-vep          : 89.7

Thanks for taking a look,
Matt


On Mon, Jan 14, 2019 at 8:15 AM Andrew Parton <aparton at ebi.ac.uk> wrote:

> Hi Matt,
>
> Upstream/Downstream consequences should be reported on the occasions where
> a variant is found to be 5’/3’ of a gene - it shouldn’t depend on
> surrounding variants within the VCF. Could you please send me an example so
> that I can reproduce it and take a closer look?
>
> Thanks,
> Andrew
>
> > On 11 Jan 2019, at 17:12, Matt Wood <matt.wood at codifiedgenomics.com>
> wrote:
> >
> > I was hoping to get some clarification on how the upstream_gene_variant
> and downstream_gene_variant consequences are determined.
> >
> > We've found several cases where a variant will have downstream or
> upstream consequences when that variant appears in one VCF, but will be
> annotated without those consequences when in another VCF.
> >
> > Our best guess is that the context of surrounding variants in the VCF is
> changing whether those consequences are applied.
> >
> > Is that how it is supposed to work? We're running version 89.7.
> >
> > Matt
> > _______________________________________________
> > Dev mailing list    Dev at ensembl.org
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