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

[Matt Wood]

Thanks for the quick update!

We'll start the upgrade process.

Matt

On Tue, Jan 15, 2019 at 5:13 AM Andrew Parton <aparton at ebi.ac.uk> wrote:

> Hi Matt,
>
> 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.
>
> Kind Regards,
> Andrew
>
> On 14 Jan 2019, at 22:16, Matt Wood <matt.wood at codifiedgenomics.com>
> wrote:
>
> 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
>> > _______________________________________________
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> <has_downstream.vcf><no_downstream.vcf>
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