ClinVar
Overview
Deprecated
ClinVar has changed to a new XML format Use CliVarPreview for latest ClinVar entries.
ClinVar is a freely accessible, public archive of reports of the relationships among human variations and phenotypes, with supporting evidence. ClinVar thus facilitates access to and communication about the relationships asserted between human variation and observed health status, and the history of that interpretation.
Publication
Melissa J Landrum, Jennifer M Lee, Mark Benson, Garth R Brown, Chen Chao, Shanmuga Chitipiralla, Baoshan Gu, Jennifer Hart, Douglas Hoffman, Wonhee Jang, Karen Karapetyan, Kenneth Katz, Chunlei Liu, Zenith Maddipatla, Adriana Malheiro, Kurt McDaniel, Michael Ovetsky, George Riley, George Zhou, J Bradley Holmes, Brandi L Kattman, Donna R Maglott, ClinVar: improving access to variant interpretations and supporting evidence, Nucleic Acids Research, 46, Issue D1, 4 January 2018, Pages D1062–D1067, https://doi.org/10.1093/nar/gkx1153
RCV File
Example
Here's a full RCV entry:
Parsing
In the following section, we discuss which field of the XML was used to extract information that is presented in the JSON output.
ID
The Acc and Version fields are merged to form the ID (RCV000000001.2)
LastUpdatedDate
Significance
ReviewStatus
Phenotypes
We only use the field with Type="Preferred". Multiple phenotypes may be reported
Location, Variant Type and Variant Id
The variant position is extracted from the fields for their respective assemblies.
Updated records contain positionVCF, referenceAlleleVCF and alternateAlleleVCF fields and when present, we use them to create the variant.
For older records, since "start' and "stop" fields are not always available, we use the "display_start" and "display_end" fields.
If a required allele is not available, we extract it from the reference sequence.
Only variants having a dbSNP id are extracted.
Note that a ClinVar accession may have multiple variants associated with it (possible in different locations)
VariantId is extracted from the MeasureSet attributes.
VariantType is extracted from the Measure attributes.
unsupported variant types
We currently don't support the following variant types:
Microsatellite
protein only
fusion
Complex
Variation
Translocation
MedGen, OMIM, Orphanet IDs
AlleleOrigins
We only extract all Allele Origins from Submissions (SCV) entries.
PubMedIds
We only extract all Pubmed Ids from Submissions (SCV) entries.
Parsing Significance
Extracting significance(s) may involve parsing multiple fields. Take the following snippets into consideration.
Given the evidence, we converted the significance field into an array of strings which may be parsed out of the Descriptions or Explanation fields.
Varying Delimiters
The delimiters in each field may vary. Currently, the delimiters for Description are , and /. The delimiters for Explanation are ; and /.
VCV File
Example
Parsing
In the following section, we discuss which field of the XML was used to extract information that is presented in the JSON output.
id
The Acc and Version fields are merged to form the ID (RCV000000001.2)
significance
May have multiple significances listed.
reviewStatus
Known Issues
Known Issues
The XML file contains ~1k more entries (out of 162K) than the VCF file
The XML file does not have a field indicating that a record is associated with the reference base - something that was present in VCF
The XML file contains entries (e.g. RCV000016645 version=1) which have IUPAC ambiguous bases ("R", "Y", "H", etc.) as their alternate allele
Download URLs
JSON Output
small variants:
large variants:
id
string
ClinVar ID
variationId
string
ClinVar VCV ID
variantType
string
variant type
reviewStatus
string
see possible values below
alleleOrigins
string array
see possible values below
refAllele
string
altAllele
string
phenotypes
string array
medGenIds
string array
MedGen IDs
omimIds
string array
OMIM IDs
orphanetIds
string array
Orphanet IDs
significance
string array
see possible values below
lastUpdatedDate
string
yyyy-MM-dd
pubMedIds
string array
PubMed IDs
isAlleleSpecific
bool
true when the current variant alternate allele matches the ClinVar alternate allele
reviewStatus:
no assertion provided
no assertion criteria provided
criteria provided, single submitter
practice guideline
classified by multiple submitters
criteria provided, conflicting interpretations
criteria provided, multiple submitters, no conflicts
no interpretation for the single variant
alleleOrigins:
unknown
other
germline
somatic
inherited
paternal
maternal
de-novo
biparental
uniparental
not-tested
tested-inconclusive
significance:
uncertain significance
not provided
benign
likely benign
likely pathogenic
pathogenic
drug response
histocompatibility
association
risk factor
protective
affects
conflicting data from submitters
other
no interpretation for the single variant
conflicting interpretations of pathogenicity
Building the supplementary files
There are 2 ways of building your own OMIM supplementary files using SAUtils.
The first way is to use SAUtils command's subcommands clinvar. The ClinVar .nsa and .nsi for Illumina Connected Annotations can be built using the SAUtils command's clinvar subcommand.
The second way is to use SAUtils command's subcommands AutoDownloadGenerate. To use AutoDownloadGenerate, read more in SAUtils section.
Using clinvar subcommands and source data files
Two input .xml files and a .version file are required in order to build the .nsa and .nsi file. You should have the following files:
The version file is a json file with the following format.
You have to adjust the version and release date according to the actual date of the ClinVar.
The help menu for the utility is as follows:
Here is a sample execution:
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