Need distance to flanking upstream and downstream exons and genes

[Sanaz01]

Hi,
I am trying to annotate my list of SNP variants using VEP in the docker container ensemblorg/ensembl-vep:release_113.3
The command line is as follows:

vep --input_file inputfiles/variants.vcf --output_file vep_results --overlaps --plugin NearestGene --plugin NearestExonJB --safe --cache --cache_version 106 --nearest=gene --fasta reference_genome.fa --numbers --total_length --biotype --protein --hgvs --hgvsg --symbol

How can I get the following information in my output file?

1. For intron_variants, report the exon IDs that flank this region and return distance to them (both upstream and downstream)
2. For intergenic_variant, report the gene IDs that flank this region and return distance to them (both upstream and downstream)

Thank you in advance!

[dglemos]

Hi @Sanaz01,

For intron_variants, report the exon IDs that flank this region and return distance to them (both upstream and downstream)

The plugin NearestExonJB returns the nearest exon junction boundary to a coding sequence variant, but it only returns one exon. However, this plugin is not designed for your specific use case, as it returns exons that overlap the variant rather than those nearest to it.
We are going to investigate if it's possible to extend the existing plugin to fit your specific requirement.

For intergenic_variant, report the gene IDs that flank this region and return distance to them (both upstream and downstream)

The plugin NearestGene reports the nearest genes to a intergenic variant both upstream and downstream.
By default it only returns one gene but that can be changed with option limit (default: 1 gene). You can also change the maximum search range with option max_range (default: 10000 bp)
The current limitation is that it only reports the gene IDs, without indicating the distance to the variant.

[Sanaz01]

Hi @dglemos
Thank you so much for you feedback. I investigated a little futher and found the following things:
CMD command

vep --input_file inputfiles/variants.vcf --output_file vep_results --overlaps --plugin NearestGene,limit=3,max_range=5000 --plugin NearestExonJB,intronic=1 --safe --cache --cache_version 106 --nearest=gene --fasta reference_genome.fa --numbers --total_length --biotype --protein --hgvs --hgvsg --symbol

1. From Update NearestExonJB VEP_plugins#771 I tested the intronic argument in NearestExonJB plugin. The output is as expected. Thank you for making the changes.
2. For variants with intergenic_variant as a consequence, can there be a quick fix to add distance to upstream and downstream gene? Perhaps something similar to the fix above?
   If this can be done, then I would use option --distance 100, to minimize upstream_gene_variant and downstream_gene_variant and increase intergenic_variant consequence. Is this a good idea? Considering I am only interested in finding whether they are in intergenic regions and their distance to genes.