ERROR: Failed to run the VEP annotator!

[neilihrke]

perl vcf2maf.pl --input-vcf /path/to/somaticvariants.vcf --output-maf /path/to/out.maf --tumor-id s_MC7562_tumor --normal-id s_MC7562_germline --vep-path /path/to/vep/94/ --vep-data /path/to/vep91/cache/files -tmp-dir /tmp/dir --ncbi-build GRCh38 --ref-fasta /path/to/ref/fastq/seqs_for_alignment_pipelines.ucsc_ids/GCA_000001405.15_GRCh38_no_alt_short_headers_nonACTG_to_N.fa --cache-version 91
STATUS: Running VEP and writing to: /output/path/somaticvariants.vep.vcf
Can't call method "db" on an undefined value at /research/bsi/tools/biotools/vep/94/Bio/EnsEMBL/Funcgen/BindingMatrix.pm line 237, <ANONIO> line 158856.
Died in forked process 83328

ERROR: Failed to run the VEP annotator! Command:

[ckandoth]

Thanks for reporting this. It looks like a VEP runtime error. It was either not installed fully or had an un-handled exception. Let me know if you are still having this issue. And please provide a sample VCF to help debug.

[mwyczalkowski]

I've had this error as well. I include VCF which caused this error as well as the error message and script in the attached .tar.gz
VEP_Annotation_error.tar.gz

[ShixiangWang]

I have same issue no matter I use conda vep or github vep when I test maf2maf

# vep install from bioconda
perl maf2maf.pl --input-maf tests/test.maf --output-maf tests/test.vep.maf -vep-path /public/data/.neopip/miniconda/share/ensembl-vep-96.0-0/ --vep-data /public/data/.neopip/vep/ --ref-fasta 
# vep clone from github
perl maf2maf.pl --input-maf tests/test.maf --output-maf tests/test.vep.maf -vep-path /public/data/.neopip/ensembl-vep --vep-data /public/data/.neopip/vep/ --ref-fasta /public/data/.neopip/vep/homo_sapiens/91_GRCh37/Homo_sapiens.GRCh37.75.dna.primary_assembly.fa --filter-vcf 0 --cache-version 91  

Return:

WARNING: Replacing '-' with reference allele in: PIK3CA 0       .       GRCh37  3       178936091       178936091       +       Missense_Mutation       SNP     G       -       A    TUMOR    NORMAL  G       G                                                                                                                               43      21      22      11   11       0
STATUS: Running VEP and writing to: /tmp/cEj9rwaUxu/test.vep.vcf
Possible precedence issue with control flow operator at /public/data/.neopip/miniconda/lib/site_perl/5.26.2/Bio/DB/IndexedBase.pm line 805.
Can't call method "db" on an undefined value at /public/data/.neopip/miniconda/share/ensembl-vep-96.0-0/Bio/EnsEMBL/Funcgen/BindingMatrix.pm line 241, <__ANONIO__> line 108.
Died in forked process 11685

ERROR: Failed to run the VEP annotator! Command: /public/data/.neopip/miniconda/bin/perl /public/data/.neopip/miniconda/share/ensembl-vep-96.0-0//vep --species homo_sapiens --assembly GRCh37 --offline --no_progress --no_stats --buffer_size 5000 --sift b --ccds --uniprot --hgvs --symbol --numbers --domains --gene_phenotype --canonical --protein --biotype --uniprot --tsl --pubmed --variant_class --shift_hgvs 1 --check_existing --total_length --allele_number --no_escape --xref_refseq --failed 1 --vcf --flag_pick_allele --pick_order canonical,tsl,biotype,rank,ccds,length --dir /public/data/.neopip/vep/ --fasta /public/data/.neopip/vep/homo_sapiens/91_GRCh37/Homo_sapiens.GRCh37.75.dna.primary_assembly.fa --format vcf --input_file /tmp/cEj9rwaUxu/test.vcf --output_file /tmp/cEj9rwaUxu/test.vep.vcf --fork 4 --cache_version 91 --polyphen b --af --af_1kg --af_esp --af_gnomad --regulatory

It is okay for vcf2maf.

Any suggestion?

Best,
Shixiang

[henry410213028]

I got similar error when using VEP

perl $(which vep) --species homo_sapiens --input_file /dev/stdin --format vcf --output_file $path_AnoVcf --stats_text /path/to/vep_stats.txt --cache --dir_cache /path/to/VEP_cache --cache_version 91 --offline --everything --vcf --vcf_info_field ANN --fasta /path/to/Homo_sapiens.GRCh38.dna_sm.primary_assembly.add_chr.fa -custom /path/to/custom.bed.gz,custom,bed,overlap,0

Can't call method "db" on an undefined value at /path/to/ensembl-vep-96.0-0/Bio/EnsEMBL/Funcgen/BindingMatrix.pm line 241, <ANONIO> line 128506.

I solve this error by change --cache-version 91 to 96
Hope it helps you

[jtbeales]

Same issue.

Can't call method "db" on an undefined value at /opt/vep/src/ensembl-vep/Bio/EnsEMBL/Funcgen/BindingMatrix.pm line 237, <ANONIO> line 119860.

I'll try tweaking --cache-version, but my error isn't exactly like the error of @henry410213028 (line 241 vs line 237 in BindingMatrix.pm).

Any updates/solutions? @ckandoth

I should also note that I'm running 26 samples. 14 run fine, but the rest crash. The jobs are iteratively submitted in a bash script, so things should be pretty standardized between them.

[SuiyueWestlake]

Hi, I got the same error.

ERROR: Failed to run the VEP annotator!

Is there any one fix this problem?

[xsvato01]

Same here, VEP crashes on most of my samples. I checked the vcf line suggested from line xxxx and it looks fine..

[xsvato01]

Ok for me worked updating the cache folder. Perhaps it got somehow corrupted