ClinVar - NCBI

Since July 2015, ClinVar modified its "star system". The new "star system" has been integrated in Alamut Visual the 29 July 2015. Please see the definitions

Alamut® Visual provides a convenient access to the NCBI ClinVar database.

ClinVar, hosted and managed by the NCBI, aggregates information about sequence variation and its relationship to human health by providing a public archive of reports of the relationships among human variations and phenotypes, with supporting evidence. More information about the ClinVar submitters is available.

ClinVar provides monthly comprehensive releases of its repository. You can see the ClinVar release used in Alamut® Visual in ClinVar detailed reports.

ClinVar visualization can be activated in the Options dialog box. (menu 'Tools' > 'Options' > 'Display' tab):

ClinVar

Alamut® Visual displays ClinVar variants in a dedicated track:

Variant background colors are based on the clinical significance provided by ClinVar submitters. (Background colors follow the scheme defined for the 5 Classes pathogenicity classification as specified in menu Tools > Options > Preferences). The default colors are:

Red for certainly pathogenic variants
Orange for likely pathogenic variants
Light Green for likely benign variants
Green for certainly benign variants
Yellow for variants of an uncertain significance

If multiple SNVs are reported at the same position a white background is displayed along with a "+" sign.

Right-clicking on a variant displays a detailed report similar to ClinVar web pages.

You can also apply filtering based on review status and/or phenotypes provided by ClinVar submitters.

Filtering variants based on review status

Clicking on stars defines your minimal review status filtering level. For instance, clicking on the third star displays variants with at least a 3-stars review status.

Since the 29 July 2015 in Alamut Visual, the ClinVar "star system" is defined as follows (current definition):

No star: No submitter provided an interpretation with assertion criteria (no assertion criteria provided), or no interpretation was provided (no assertion provided).
1 star: At least one submitter provided an interpretation with assertion criteria (criteria provided, single submitter) or multiple submitters provided assertion criteria but there are conflicting interpretations in which case the independent values are enumerated for clinical significance (criteria provided, conflicting interpretations).
2 stars: Two or more submitters providing assertion criteria provided the same interpretation (criteria provided, multiple submitters, no conflicts).
3 stars: Reviewed by expert panel.
4 stars: Practice guideline.

The ClinVar "star system" definition was as defined below until 29 July 2015 in Alamut Visual:

No star: Either conficting interpretations (in which case the independent values are enumerated), or no submitter provided an interpretation.
1 star: One submitter provided an interpretation (classified by single submitter).
2 stars: Two or more submitters provided the same interpretation (classified by multiple submitters).
3 stars: Reviewed by expert panel.
4 stars: Practice guideline.

Filtering variants based on phenotype

References

Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014 Jan 1;42(1):D980-5. doi: 10.1093/nar/gkt1113. PubMed PMID: 24234437
Melissa Landrum, PhD, Jennifer Lee, PhD, George Riley, PhD, Wonhee Jang, PhD, Wendy Rubinstein, MD, PhD, Deanna Church, PhD, and Donna Maglott, PhD. ClinVar. NBK174587