ClinVar Miner

Submissions for variant NM_004820.5(CYP7B1):c.1354C>T (p.Arg452Ter)

dbSNP: rs769676029
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
GeneDx RCV000578856 SCV000681166 likely pathogenic not provided 2017-12-04 criteria provided, single submitter clinical testing The R452X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R452X variant is a nonsense variant in the C-terminus predicted to result in protein truncation, as the last 55 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014). The R452X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Paris Brain Institute, Inserm - ICM RCV001391411 SCV001451303 pathogenic Hereditary spastic paraplegia 5A criteria provided, single submitter clinical testing
Invitae RCV003767256 SCV004685475 pathogenic Spastic paraplegia 2023-11-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg452*) in the CYP7B1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 55 amino acid(s) of the CYP7B1 protein. This variant is present in population databases (rs769676029, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CYP7B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 489179). This variant disrupts a region of the CYP7B1 protein in which other variant(s) (p.Arg486Cys) have been determined to be pathogenic (PMID: 19439420, 21623769, 23812641, 24117163). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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.