Submissions for variant NM_004820.5(CYP7B1):c.125G>A (p.Arg42Lys)

gnomAD frequency: 0.00007  dbSNP: rs375384257

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000353958	SCV000343246	uncertain significance	not provided	2016-06-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000321175	SCV000474717	uncertain significance	Hereditary spastic paraplegia 5A	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001321782	SCV001512626	uncertain significance	Spastic paraplegia	2022-08-23	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 42 of the CYP7B1 protein (p.Arg42Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 288985). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Revvity Omics, Revvity	RCV000353958	SCV003830399	uncertain significance	not provided	2022-06-08	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000353958	SCV004035188	uncertain significance	not provided	2018-07-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003417908	SCV004108816	uncertain significance	CYP7B1-related condition	2024-01-03	criteria provided, single submitter	clinical testing	The CYP7B1 c.125G>A variant is predicted to result in the amino acid substitution p.Arg42Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.087% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.