ClinVar Miner

Submissions for variant NM_000497.3(CYP11B1):c.1120C>A (p.Arg374=) (rs61752786)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000454869 SCV000052289 likely benign not specified 2019-09-10 criteria provided, single submitter clinical testing Variant summary: CYP11B1 c.1120C>A (p.Arg374Arg) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools via ALAMUT predict no significant impact on normal splicing. Another tool for predicting the outcome of synonymous variants, namely Transcript-inferred Pathogenicity score (TraP, Gelfman_2017) predicts this variant to be possibly pathogenic. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.017 in 248518 control chromosomes in the gnomAD database, including 57 homozygotes. The observed variant frequency is approximately 8.5 fold the estimated maximal allele frequency expected for a pathogenic variant in CYP11B1 causing Congenital Adrenal Hyperplasia phenotype (0.002), strongly suggesting that the variant is benign. c.1120C>A has been reported in the literature in individuals affected with Congenital Adrenal Hyperplasia, but without strong evidence for causality (Dundar_2019). This report does not provide unequivocal conclusions about association of the variant with Congenital Adrenal Hyperplasia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000029637 SCV000472330 likely benign Deficiency of steroid 11-beta-monooxygenase 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000397180 SCV000472331 benign Hyperaldosteronism, familial, type I 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000454869 SCV000538763 benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (too high for associated disease - congenital adrenal hyperplasia)
Athena Diagnostics Inc RCV000711393 SCV000841756 benign not provided 2017-11-24 criteria provided, single submitter clinical testing
Department of Human Genetics,Laborarztpraxis Dres. Walther, Weindel und Kollegen RCV000029637 SCV001424544 likely benign Deficiency of steroid 11-beta-monooxygenase 2020-04-20 criteria provided, single submitter clinical testing

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