ClinVar Miner

Submissions for variant NM_000497.4(CYP11B1):c.187G>C (p.Asp63His)

gnomAD frequency: 0.00001  dbSNP: rs5282
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668553 SCV000793175 uncertain significance Deficiency of steroid 11-beta-monooxygenase 2017-07-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282305 SCV002572290 likely pathogenic Congenital adrenal hyperplasia 2024-05-03 criteria provided, single submitter clinical testing Variant summary: CYP11B1 c.187G>C (p.Asp63His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251400 control chromosomes.c.187G>C has been reported in the literature in at least one individual affected with Congenital Adrenal Hyperplasia, although in cis with a frameshift variant (e.g. Long_2016). This report not provide unequivocal conclusions about association of the variant with Congenital Adrenal Hyperplasia. At least one publication reports experimental evidence evaluating an impact on protein function, with COS-7 cells transfected with the variant showing 2% enzyme activity compared to ,cells transfected with wild-type (e.g. Long_2016). The following publication has been ascertained in the context of this evaluation (PMID: 26806323). ClinVar contains an entry for this variant (Variation ID: 553163). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV005091936 SCV005776578 uncertain significance not provided 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 63 of the CYP11B1 protein (p.Asp63His). This variant is present in population databases (rs5282, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CYP11B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 553163). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CYP11B1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.