Convert MacArthur ClinVar TSV to VCF

This script will (1.) download the latest release of MacArthur Lab's version of ClinVar in TSV format and (2.) convert it to a VCF file.

Output

The output will be a VCF file (compressed and indexed if possible). The MacArthur Lab splits and left-aligns their TSV file, so in turn, the output VCF will also be split and left-aligned. There is no need for further normalization with BCFtools.

The INFO column will contain the following tags:

CLINVAR_CLNALLELE - Tells you which allele, REF or ALT, is the one to which the annotations (e.g. pathogenic assertion) refer
CLINVAR_VID - Variation ID; unique identifier for the set of sequence changes that were interpreted; access online at ncbi.nlm.nih.gov/clinvar/variation/{VID}
CLINVAR_HGNC - HGNC gene symbol
CLINVAR_CLNSIG - Clinical significance (e.g. "Pathogenic", "Likely pathogenic", etc.)
CLINVAR_REVSTAT - Clinical review status
CLINVAR_HGVS_C - HGVS cDNA name
CLINVAR_HGVS_P - HGVS protein name
CLINVAR_SUBMITTERS - The names of clinical review submitters
CLINVAR_DISEASE - Variant disease name(s)
CLINVAR_PMID - Related PubMed IDs
CLINVAR_PATHOGENIC - Has this variant been asserted 'Pathogenic' or 'Likely pathogenic' by any submitter for any phenotype? 1 - Yes, 0 - No
CLINVAR_CONFLICTED - Has this variant ever been asserted 'Pathogenic' or 'Likely pathogenic' by any submitter for any phenotype and also been asserted 'Benign' or 'Likely benign' by any submitter for any phenotype? 1 - Yes, 0 - No; Note that having one assertion of pathogenic and one of uncertain significance does not count as conflicted for this column

Usage

Simply run:

./get_newest_ClinVar_from_MacArthur.sh

What is info_tag_map.txt?

This is a map file that get_newest_ClinVar_from_MacArthur.sh automatically looks for when converting the original TSV file to a VCF file. It contains 3 tab-separated columns:

Column 1: Names of the columns in the original TSV file
Column 2: Descriptions to use for the corresponding INFO tag in the output VCF file
Column 3: Preferred names of the respective INFO tags in the output VCF file

For example:

 symbol      HGNC gene symbol    HGNC
 hgvs_c      HGVS cDNA name      HGVS_C
 hgvs_p      HGVS protein name   HGVS_P
 all_pmids   PubMed IDs          PMID

All INFO tags will automatically be prefixed with the CLINVAR_ string when the VCF file is written. If a

Handling illegal VCF characters

The VCF format restricts all spaces, semi-colons, and equals-signs from being present in an any INFO field. Additionally, commas are reserved for separating allele-specific values. Therefore, these characters are URL-encoded before they are written to the output VCF.

Illegal VCF character	URL-encoding
space	%20
,	%2C
;	%3B
=	%3D

Requirements

tab2vcf must be in your $PATH (download it here). VCF conversion will be skipped if this is not found.
bgzip and tabix must both be in your $PATH (download with the HTSlib package here). If one or both of these are not found, then compression and indexing will be skipped.

Author

Sean Ephraim

sephraim / convert_MacArthur_ClinVar_TSV_to_VCF