ClinVar: public archive of relationships among sequence variation and human phenotype

By M. Landrum, Jennifer M. Lee, George R. Riley, W. Jang, W. Rubinstein, D. Church, Donna R. Maglott. 2013

3,237 citations recorded by the source corpus.

ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations.

Subfields: Genetics, Molecular Biology, Computational Biology & Bioinformatics

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Citations in the corpus

CADD: predicting the deleteriousness of variants throughout the human genome (2018, critical): “Akeystrength of CADD is that the model is trained on a very large training set that does not suffer from ascertainment bias inherent to curated sets of pathogenic and benign variants such as ClinVar (7) or HGMD (58).”
Evolved Cas9 variants with broad PAM compatibility and high DNA specificity (2018, positive): “Indeed, compared to SpCas9–BE3, xCas9(3.7)–BE3 increases the percentage of 4,422 pathogenic SNPs in the ClinVar database 38 that in principle could be targeted by C•G to T•A base editing from 26% to 73% (Fig.”
Quantitative missense variant effect prediction using large-scale mutagenesis data (2017, positive): “Finally, we assessed the utility of Envision scores for clinical effect prediction, evaluating performance by constructing receiver-operating characteristic (ROC) curves using variants annotated as either pathogenic or benign in ClinVar.”
Finding Our Way through Phenotypes (2015, background): “example, the NCBI databases [7,44] capture data concerning human variants”
Bridging semantics and syntax with graph algorithms —state-of-the-art of extracting biomedical relations (2015, background): “Others are more clinically focused, such as PharmGKB [12], VARIMED [13] and ClinVar [14].”
Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR (2015, background): “) 52 and ‘snp138’ for the dbSNP database (version 138) 53 .”
A Whole-Genome Analysis Framework for Effective Identification of Pathogenic Regulatory Variants in Mendelian Disease. (2016, methodology): “Moreover, in each partition we synthetically oversampled the minority positive class, using the synthetic minority over-sampling technique 51 (SMOTE) with a number of nearest neighbors k ¼ 5.”
SRAMP: prediction of mammalian N6-methyladenosine (m6A) sites based on sequence-derived features (2016, background): “It was reported that a mutation of its upstream G to C (rs387906584) results in APRT deficiency which makes patients vulnerable to kidney and urinary tract stone (43,44).”
The Polygenic and Monogenic Basis of Blood Traits and Diseases (2020, methodology): “Similarly, we found apparently healthy homozygous carriers for other four recessive variants, reported as pathogenic in HGMD, but not in ClinVar (rs61755431 in PKLR for pyruvate kinase deficiency or red cells, rs138156467 in CSF3R for neutropenia, rs61745086 in PIEZO1 for dehydrated stomatocytosis a”