WARNING: Chromosome 22 not found in annotation sources or synonyms on line 1

[MaayanYoles]

Describe the issue

Hi, I am trying to use VEP for the first time and after successfully installing. I downloaded an older version (105). when running the tool i get an error about the chromosome in my vcf file.

The tool does make the .txt file and the txt_summary.html file, but they are empty and there is an additional file of txt_warnings.txt that has one line: WARNING: Chromosome 22 not found in annotation sources or synonyms on line 1

I will say the vcf file being used was make using bcftools and PLINK.

the vcf's header looks like this, and has the chromosome number in it:

fileformat=VCFv4.2

fileDate=20240222

source=PLINKv1.90

contig=

INFO=

FORMAT=

CHROM POS ID REF ALT QUAL FILTER INFO FORMAT

thank you so much Maayan

System

• VEP version: [105]
• VEP Cache version: [105]
• Perl version: [v5.16.3]
• OS: [lynux]
• tabix installed yes

Full VEP command line

vep --format vcf -i .vep/DATA_all_00_hg19_chr_22_16000000_17000000.vcf -o .vep/vep_DATA_all_00_hg19_chr_22_16000000_17000000.txt --offline --force_overwrite

[olaaustine]

Hi @MaayanYoles, Hope you are well? Thank you for your query. To use offline mode, an additional source of annotation is required. See here. If you have the cache files already downloaded, please point to the directory using --dir_cache. If the cache files have not been downloaded yet, please see here to manually download our cache files. Let us know if this helps. Thank you very much Ola.

[MaayanYoles]

Hi @olaaustine,

Thank you so much for the response!

I have downloaded the cache file and have it in the VEP folder under the correct path (.vep/homo_sapiens/105_GRCh37.tar). When i use the --dir_cache with the full path

--dir_cache .vep/homo_sapiens/105_GRCh37.tar

I get the following error and there are no files made by the tool: MSG: ERROR: Cache directory .vep/homo_sapiens/105_GRCh37.tar/homo_sapiens not found and when I use

--dir_cache .vep 

there is a result file made, with the following error: WARNING: Chromosome 22 not found in annotation sources or synonyms on line 1

so I think maybe the issue is not the cache file

[olaaustine]

Hi @MaayanYoles, Thank you for your response. Please follow the instructions here

cd  .vep/homo_sapiens/
tar -xvf 105_GRCh37.tar

Your cache directory should be <homo_sapiens>/<105_GRCh37>not .tar Please let us know if this helps. Thank you so much Ola.

[olaaustine]

Hi @MaayanYoles, Just a follow up about this issue. Thank you Ola.

[MaayanYoles]

Hi @olaaustine, Thank you for the follow up, I appreciate it.

When following your instructions I get a long output looking like this:

homo_sapiens/105_GRCh37/Y/6000001-7000000_reg.gz
homo_sapiens/105_GRCh37/Y/7000001-8000000.gz
homo_sapiens/105_GRCh37/Y/7000001-8000000_reg.gz
homo_sapiens/105_GRCh37/Y/8000001-9000000.gz
homo_sapiens/105_GRCh37/Y/8000001-9000000_reg.gz
homo_sapiens/105_GRCh37/Y/9000001-10000000.gz
homo_sapiens/105_GRCh37/Y/9000001-10000000_reg.gz

And in this output I can see there is data for chr22. Nevertheless, when I use the tool I still end up with the same issue : when running like you suggested

--dir_cache .vep/homo_sapiens/105_GRCh37

I get an error and no files made - " ERROR: Cache directory .vep/homo_sapiens/105_GRCh37/homo_sapiens not found" and when i run this shorter command:

--dir_cache .vep

I get the warning about chromosome 22 not found, but output files are being made.

Thanks again, Maayan

[olaaustine]

Hi @MaayanYoles, Hope you are well? To debug this issue, can you confirm that you have tabix installed in your path? If you do, can you go into this directory.vep/homo_sapiens/105_GRCh37 and confirm that you have chr_synonyms.txt and you should have the directory structurehomo_sapiens/105_GRCh37/<chromosome_number/name> Thank you Ola.

[MaayanYoles]

Hi @olaaustine I am well, hope you are too.

I followed your instructions and it worked!! The results look great and the tool runs. Thank you so much for the patience.

Have a great day :) Maayan

[olaaustine]

Hi @MaayanYoles, I am well, thank you 😁 Thank you for letting us know and thank you for using VEP. I will close this ticket now, please feel free to reopen this or open another ticket if you have any issues. Do have a lovely day. Thank you, Ola