<html><head><meta http-equiv="Content-Type" content="text/html; charset=utf-8"></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; line-break: after-white-space;" class="">Hi Matt,<div class=""><br class=""></div><div class="">Thanks for these, we’ve taken a quick look this morning and we can reproduce the issue. It looks like this is a problem specific to r89 of VEP, updating VEP to the latest version (95) should resolve this issue.</div><div class=""><br class=""></div><div class="">Kind Regards,</div><div class="">Andrew<br class=""><div><br class=""><blockquote type="cite" class=""><div class="">On 14 Jan 2019, at 22:16, Matt Wood <<a href="mailto:matt.wood@codifiedgenomics.com" class="">matt.wood@codifiedgenomics.com</a>> wrote:</div><br class="Apple-interchange-newline"><div class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class="">I've managed to put together a small example with two variants that show the behavior. I've attached two vcfs.<div class=""><br class=""></div><div class="">The variant we're looking at is 22:35998183TTGTGTC>T.</div><div class=""><br class=""></div><div class="">I've found I can reproduce the bug with just the following options:</div><div class=""><br class=""></div><div class="">perl /space1/software/vep/ensembl-vep/vep --dir /vep/cache/ --offline --vcf --regulatory -i has_downstream.vcf -o has_downstream.vcf.vep<br class=""></div><div class=""><br class=""></div><div class="">If you run it on no_downstream.vcf we're getting the following output:<br class=""></div><div class=""><br class=""></div><div class="">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 class=""></div><div class=""><br class=""></div><div class="">But, if we run it on has_downstream.vcf we get additional downstream effects for the variant we're looking at:</div><div class=""><br class=""></div><div class="">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 class=""></div><div class=""><br class=""></div><div class="">The only difference being the addition of another variant in the vcf.</div><div class=""><br class=""></div><div class="">Our version info:</div><div class=""><br class=""></div><div class=""><div class="">Versions:</div><div class=""> ensembl : 89.df47f96</div><div class=""> ensembl-funcgen : 89.678099a</div><div class=""> ensembl-io : 89.feefbc2</div><div class=""> ensembl-variation : 89.af9aae5</div><div class=""> ensembl-vep : 89.7</div></div><div class=""><br class=""></div><div class="">Thanks for taking a look,</div><div class="">Matt</div><div class=""><br class=""></div></div></div></div></div></div></div></div></div><br class=""><div class="gmail_quote"><div dir="ltr" class="">On Mon, Jan 14, 2019 at 8:15 AM Andrew Parton <<a href="mailto:aparton@ebi.ac.uk" target="_blank" class="">aparton@ebi.ac.uk</a>> wrote:<br class=""></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 class="">
<br class="">
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 class="">
<br class="">
Thanks,<br class="">
Andrew<br class="">
<br class="">
> On 11 Jan 2019, at 17:12, Matt Wood <<a href="mailto:matt.wood@codifiedgenomics.com" target="_blank" class="">matt.wood@codifiedgenomics.com</a>> wrote:<br class="">
> <br class="">
> I was hoping to get some clarification on how the upstream_gene_variant and downstream_gene_variant consequences are determined.<br class="">
> <br class="">
> 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 class="">
> <br class="">
> Our best guess is that the context of surrounding variants in the VCF is changing whether those consequences are applied.<br class="">
> <br class="">
> Is that how it is supposed to work? We're running version 89.7.<br class="">
> <br class="">
> Matt<br class="">
> _______________________________________________<br class="">
> Dev mailing list <a href="mailto:Dev@ensembl.org" target="_blank" class="">Dev@ensembl.org</a><br class="">
> Posting guidelines and subscribe/unsubscribe info: <a href="http://lists.ensembl.org/mailman/listinfo/dev" rel="noreferrer" target="_blank" class="">http://lists.ensembl.org/mailman/listinfo/dev</a><br class="">
> Ensembl Blog: <a href="http://www.ensembl.info/" rel="noreferrer" target="_blank" class="">http://www.ensembl.info/</a><br class="">
<br class="">
_______________________________________________<br class="">
Dev mailing list <a href="mailto:Dev@ensembl.org" target="_blank" class="">Dev@ensembl.org</a><br class="">
Posting guidelines and subscribe/unsubscribe info: <a href="http://lists.ensembl.org/mailman/listinfo/dev" rel="noreferrer" target="_blank" class="">http://lists.ensembl.org/mailman/listinfo/dev</a><br class="">
Ensembl Blog: <a href="http://www.ensembl.info/" rel="noreferrer" target="_blank" class="">http://www.ensembl.info/</a><br class="">
</blockquote></div>
<span id="cid:f_jqwuvyk31"><has_downstream.vcf></span><span id="cid:f_jqwuvyju0"><no_downstream.vcf></span>_______________________________________________<br class="">Dev mailing list <a href="mailto:Dev@ensembl.org" class="">Dev@ensembl.org</a><br class="">Posting guidelines and subscribe/unsubscribe info: <a href="http://lists.ensembl.org/mailman/listinfo/dev" class="">http://lists.ensembl.org/mailman/listinfo/dev</a><br class="">Ensembl Blog: <a href="http://www.ensembl.info/" class="">http://www.ensembl.info/</a><br class=""></div></blockquote></div><br class=""></div></body></html>