Submissions for variant NM_000784.4(CYP27A1):c.438G>A (p.Pro146=)

gnomAD frequency: 0.06494  dbSNP: rs692003

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000251233	SCV000305518	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000056115	SCV000427464	benign	Cholestanol storage disease	2018-01-13	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.
Athena Diagnostics	RCV000251233	SCV000613051	benign	not specified	2017-06-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000839224	SCV000981111	benign	not provided	2018-04-24	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000056115	SCV001718505	benign	Cholestanol storage disease	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002326779	SCV002632537	benign	Cardiovascular phenotype	2019-07-05	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Breakthrough Genomics, Breakthrough Genomics	RCV000839224	SCV005244561	benign	not provided		criteria provided, single submitter	not provided
GeneReviews	RCV000056115	SCV000087193	non-pathogenic	Cholestanol storage disease	2013-08-01	no assertion criteria provided	curation	Converted during submission to Benign.
Natera, Inc.	RCV000056115	SCV001455783	benign	Cholestanol storage disease	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000251233	SCV001917696	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000251233	SCV001954573	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000251233	SCV002036550	benign	not specified		no assertion criteria provided	clinical testing