Inconsistent HGNC:ID results between single-thread and multi-thread in vep

[karlestira]

Describe the issue

vep give different result when using multi-thread(--fork).

problem:
Some gene(like ENSG00000169047 or ENSG00000168769) will loss its refseq HGNC ID(near field EntrezGene) when using --fork, and they are shown in single-thread result.

Additional information

This inconsistent is due to the thread setting, same threads give same results bewteen different running, but different threads setting lead to different result.

I believe this is a multi-thread inconsistent bug. And I think this bug happens widely, Any WES vcf and VEP merged cache can reproduce the problem, no specific inputs need.

System

• VEP version: 112.0(conda build: pl5321h2a3209d_0, conda channel: anaconda/cloud/bioconda)
• VEP Cache version: homo_sapiens_merged/112_GRCh37
• Perl version: 5.32.1
• OS: Debian GNU/Linux 10 (buster)
• tabix installed ? tabix 1.20 from conda

Full VEP command line

vep --input_file test.vcf --output_file test.vep.10.vcf --format vcf --vcf --symbol --biotype --hgvs --fasta ucsc.hg19.fa --offline --cache --dir_cache /opt/vep/database --no_stats --merged --fork 10 --buffer_size 10000

info line in output vcf:
##VEP="v112.0" API="v112" time="2024-09-26 17:00:31" cache="/opt/vep/database/homo_sapiens_merged/112_GRCh37" ensembl=112.7104005 ensembl-funcgen=112.be19ffa ensembl-io=112.2851b6f ensembl-variation=112.4113356 1000genomes="phase3" COSMIC="98" ClinVar="202306" HGMD-PUBLIC="20204" assembly="GRCh37.p13" dbSNP="156" gencode="GENCODE 19" genebuild="2011-04" gnomADe="r2.1" polyphen="2.2.2" refseq="105.20220307 - GCF_000001405.25_GRCh37.p13_genomic.gff" regbuild="1.0" sift="sift5.2.2"

Full error message

No error message.

[likhitha-surapaneni]

Hi @karlestira,
Unfortunately I am not able to reproduce this issue on my end. Is there a specific test input file that can be shared to help us debug this?

Kind regards,
Likhitha

[karlestira]

Hi @karlestira, Unfortunately I am not able to reproduce this issue on my end. Is there a specific test input file that can be shared to help us debug this?

Kind regards, Likhitha

vcf is from vardict, and some pre-process has been done.

cmd:
5 threads:
vep --input_file NA12878L1.vardict.head10000.vcf --output_file NA12878L1.vep.5.head10000.vcf --format vcf --vcf --symbol --biotype --hgvs --fasta ucsc.hg19.fa --offline --cache --dir_cache vep_db --no_stats --merged --fork 5 --buffer_size 10000
10 threads:
vep --input_file NA12878L1.vardict.head10000.vcf --output_file NA12878L1.vep.10.head10000.vcf --format vcf --vcf --symbol --biotype --hgvs --fasta ucsc.hg19.fa --offline --cache --dir_cache vep_db --no_stats --merged --fork 10 --buffer_size 10000

using VEP database download from ftp(sorry I forgot the url) with the name: homo_sapiens_merged_vep_112_GRCh37.tar.gz

then:
diff NA12878L1.vep.5.head10000.vcf NA12878L1.vep.10.head10000.vcf

In my system, the diff is between line 62(the cmd line, it is no problem), 4892, 4893, 4987, 4988(these 4 lines is different in HGNC ID when transcript is from refseq)

NA12878L1.vardict.head10000.vcf.gz

[TimD1]

I have encountered the same issue, using VEP version 111.0.