The ClinVar variation report

The ClinVar variation report displays information from submitters aggregated by each variant (e.g. VCV123456789.1), rather than by the combination of variation-condition that is represented by the reference ClinVar accession (e.g. RCV123456789.1).  The variation display makes it easier to review what has been submitted per simple or complex allele, combining data that submitters may have provided with different disease names.

ClinVar defines a variation as the set of sequence changes about which an interpretation has been submitted. In other words, a "variation" may represent a single variant, a compound heterozygote, or a haplotype.

Title

The title represents the preferred name of the variation (Figure 1A).

  • For sequence variants within a gene, the name is constructed from the gene symbol and the HGVS expressions for the coding DNA and protein changes.
  • For sequence variants that are larger than a gene, the name is the HGVS expression for the genomic DNA change.
  • For structural variants, the name is constructed from the genome assembly name, cytogenetic location, genomic coordinates, and copy number, e.g.  GRCh38/hg38 1p31.1(chr1:71691191-72250907)x1

Figure 1.  The Title, Interpretation, and Variant details sections.

ClinVar variation report - title, interpretation, and allele sections

Interpretation

The top section reports the overall interpretation of a variation based on aggregating data from submitters (Figure 1B).  The details of what each submitter provided are listed in the Submitted interpretations and evidence section (Figure 4).

In the the variation report, the value reported for clinical significance for Mendelian disorders is based on a 3-level scale. Please see our detailed description of the representation of clinical significance in ClinVar and other variation resources at NCBI .

The values ClinVar and GTR use for clinical significance are maintained on GTR's ftp site.

https://ftp.ncbi.nlm.nih.gov/pub/GTR/standard_terms/Clinical_significance.txt

Review status (stars)

ClinVar reports the level of review supporting the assertion of clinical significance for the variation as review status. Stars provide a graphical representation of the review status on web pages. Please see our detailed description of the ClinVar review status.

Submissions

Count of submissions for the variant and the date of the most recent submission. Note: this is the total count, not the count of submissions providing an interpretation. Thus the total number of submissions may be higher than suggested by the review status.

Last evaluated

The most recent date that the variant was interpreted, or evaluated, by a submitter.

Accession

The VCV accession and version number. Read more about ClinVar's accession numbers.

Variation ID

The Variation ID is a unique identifier for the set of sequence changes that were interpreted. In other words, if the variation report is for a haplotype defined by five SNPs, there is a single Variation ID that represents that combination of SNPs in cis. Each individual SNP is represented by an Allele ID (see the Allele Description section).

Description

A brief description of the type of variant. - Short variants are described by the type of variant, e.g. single nucleotide variant or deletion. - CNVs are described by an estimate of the size and the type of variant, e.g. 597.8kb copy number gain. - Combinations of variants are described as either Haplotype or Genotype.

Variant details

The Variant details tab (Figure 1C) summarizes information about the variant, or set of variants, that was interpreted.

The Allele ID is an identifier for each individual nucleotide change in the set of variants that were interpreted. In other words, if the variation report is for interpretation of a haplotype defined by five SNPs, each SNP has its own Allele ID. The set of SNPs that make up the haplotype are represented by the Variation ID.

The Variant details tab reports names and HGVS representations, with links to other data sources about the variant itself.  The data in the Variant details section may come from submitters, but may also be added by NCBI, especially when the variant can be mapped to the genome.  Data usually provided by NCBI include:

  • the type and length of the variant
  • cytogenetic and genomic locations
  • HGVS expressions:
    • on the current and previous chromosome sequence (NC accession)
    • on current NM/NPs and RefSeqGene (NG)
    • provided by submitters
  • molecular consequence: a calculation of the effect of the sequence change, reported per transcript. ClinVar calculates the predicted molecular consequence, but does not predict functional consequence. Functional consequence (e.g. quantitative effects on gene expression, alternative splicing) is based on experimental evidence and must be submitted.
  • the protein change, if applicable
  • other names for the variant, e.g. deltaF508
  • GMAF, the global minor allele frequency calculated by the 1000 Genomes Project
  • allele frequency, with the source of the frequency data and the frequency of the stated allele
  • links to related databases, such as dbSNP, dbVar, Variation Viewer, and LSDBs (locus-specific databases)

Conditions

The Conditions tab (Figure 2) provides a summary of condition-specific interpretations for the variant, including a link to the reference ClinVar record (RCV accession).

This tab also includes a summary of all clinical features that were observed in individuals with this variant and reported to ClinVar. More information about clinical features, including the submitter, are available on the Evidence details page.

Figure 2.  The Conditions tab.

ClinVar variation report - the conditions tab

Genes

The Genes tab (Figure 3) provides a summary of information about each gene affected by the variant. Most variants in ClinVar are short and are within a single gene so the Genes tab shows data for a single gene. CNVs may affect more than one gene; in this case, the genes tab displays the first ten genes, with preference given to genes that are curated on the ClinGen Dosage Sensitivity Map. If the CNV affects more than ten genes, there are links to NCBI's Variation Viewer, the UCSC browser, and the ClinGen Dosage Sensitivity Map to view all the genes.

The links for Related variants show you other variants from this gene in ClinVar. The link for "Within gene" shows you variants that affect only this gene, mostly short variants. The link for "All" shows you any variant that affects this gene, including both short variants and CNVs.

Figure 3.  The Genes tab.

ClinVar variation report - the Genes tab

Submitted interpretations and evidence

The Submitted interpretations and evidence section (Figure 4) provides a summary of data from the submitted records for the variant. The data in the columns are taken directly from the submitted record, i.e. these data are not aggregated by ClinVar.

Table 2. Columns in the Submitted interpretations and evidence table

Column title Explanation
Interpretation (Last evaluated) The interpretation of clinical significance, with the date when the significance was last assessed (optional).

Interpretations from SCRP are submitted as individual reports which are aggregated by ClinVar. The most recent interpretation is reported on the ClinVar record; previous interpretations from SCRP are available from the "History" link.
Review status (Assertion criteria) The review status of the submitted record.  Note in this example, there are data from ACMG (professional society), CFTR2 (an expert panel), and individual submitters.

The criteria used to interpret the clinical significance is reported as Assertion criteria. This column also displays the collection method, e.g. Method: clinical testing.
Condition(s) (Inheritance) The name of the condition about which the significance of the variant is being asserted, as submitted. 

Mode of inheritance is reported as submitted to indicate the mode of inheritance used to evaluate the significance.

For pharmacogenomic variants, the condition for which the drug is used is also displayed.

This column also displays the allele origin, e.g. Allele origin: germline.
Submitter The name of the submitting organization, the accession and version number for their submitted record, and the latest date that submitter provided information for this record.

This column also displays general comments about the record.
Supporting information This column includes summary information about the evidence for the interpretation, and links to an evidence table with more detailed information. The "See all" link displays the evidence table for all submitted records for the variant; use the "Evidence details" link on a single row to see evidence from a single submission.

This column also includes links to Publications, the comment on clinical significance, and links to other databases, all as submitted.

Figure 4. The Submitted interpretations and evidence table

ClinVar variation report - the Submitted interpretations and evidence table

Citations

The Citations table lists publications about the variant. The vast majority of citations are provided by submitters; a small number have been curated by NCBI staff. Citations can be provided in several places in submissions; this table includes all citations except for those submitted on the condition and citations submitted as assertion criteria.

Dates

The date shown at the bottom of a ClinVar record, "Record last updated", represents the latest date that the aggregate record, the VCV, was last updated. The update could be due to updates in one of the submitted records (SCVs) for the VCV record, or it could be due to updates that NCBI made to the VCV record, such as adding an rs number or curating HGVS expressions.

Other dates reported on the page include:

  • the date of the most recent submission, in the Interpretation section
  • the date that the variant was most recently evaluated by a submitter, in the Interpretation section
  • the date that each submitter last evaluated the variant, in the section for Submitted interpretations and evidence
  • the date that each record was submitted to ClinVar, in the section for Submitted interpretations and evidence

Evidence details

The Evidence details page displays many of the values displayed in the table for "Submitted interpretations and evidence", along with many more detailed data types. The data are presented as a table so that you can scan across multiple submissions for the same type of data.

A few columns are shown by default. Use the "Choose Columns" button at the lower left of the table to add more columns. Many of these data types are optional in submission so you may see empty columns. One approach is to add all columns to the display to see if data was submitted for any of the optional fields.

Feedback

We continue to make improvements to these pages. Please use the green Feedback button to let us know what improvements you'd like to see.

Support Center

Last updated: 2020-03-23T21:19:48Z