<div dir="ltr"><div dir="ltr"><div dir="ltr"><div dir="ltr"><div dir="ltr"><div dir="ltr"><div dir="ltr"><div dir="ltr">I've managed to put together a small example with two variants that show the behavior. I've attached two vcfs.<div><br></div><div>The variant we're looking at is 22:35998183TTGTGTC>T.</div><div><br></div><div>I've found I can reproduce the bug with just the following options:</div><div><br></div><div>perl /space1/software/vep/ensembl-vep/vep --dir /vep/cache/ --offline --vcf --regulatory -i has_downstream.vcf -o has_downstream.vcf.vep<br></div><div><br></div><div>If you run it on no_downstream.vcf we're getting the following output:<br></div><div><br></div><div>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:.<br></div><div><br></div><div>But, if we run it on has_downstream.vcf we get additional downstream effects for the variant we're looking at:</div><div><br></div><div>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:.<br></div><div><br></div><div>The only difference being the addition of another variant in the vcf.</div><div><br></div><div>Our version info:</div><div><br></div><div><div>Versions:</div><div> ensembl : 89.df47f96</div><div> ensembl-funcgen : 89.678099a</div><div> ensembl-io : 89.feefbc2</div><div> ensembl-variation : 89.af9aae5</div><div> ensembl-vep : 89.7</div></div><div><br></div><div>Thanks for taking a look,</div><div>Matt</div><div><br></div></div></div></div></div></div></div></div></div><br><div class="gmail_quote"><div dir="ltr">On Mon, Jan 14, 2019 at 8:15 AM Andrew Parton <<a href="mailto:aparton@ebi.ac.uk" target="_blank">aparton@ebi.ac.uk</a>> wrote:<br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex">Hi Matt, <br>
<br>
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?<br>
<br>
Thanks,<br>
Andrew<br>
<br>
> On 11 Jan 2019, at 17:12, Matt Wood <<a href="mailto:matt.wood@codifiedgenomics.com" target="_blank">matt.wood@codifiedgenomics.com</a>> wrote:<br>
> <br>
> I was hoping to get some clarification on how the upstream_gene_variant and downstream_gene_variant consequences are determined.<br>
> <br>
> 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. <br>
> <br>
> Our best guess is that the context of surrounding variants in the VCF is changing whether those consequences are applied.<br>
> <br>
> Is that how it is supposed to work? We're running version 89.7.<br>
> <br>
> Matt<br>
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