ClinVar Miner

Submissions for variant NM_004820.5(CYP7B1):c.1162C>T (p.Arg388Ter)

gnomAD frequency: 0.00001  dbSNP: rs72554620
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000800899 SCV000940642 pathogenic Spastic paraplegia 2023-09-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg388*) in the CYP7B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP7B1 are known to be pathogenic (PMID: 9802883, 19363635, 19439420, 21541746, 21567895, 28039895). This variant is present in population databases (rs72554620, gnomAD 0.005%). This premature translational stop signal has been observed in individuals with hereditary spastic paraplegia and neonatal liver failure (PMID: 9802883, 18252231, 19812052). ClinVar contains an entry for this variant (Variation ID: 6100). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000006474 SCV001367373 pathogenic Hereditary spastic paraplegia 5A 2020-02-27 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS4_MOD,PM2.
Paris Brain Institute, Inserm - ICM RCV000006474 SCV001451298 pathogenic Hereditary spastic paraplegia 5A criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000006474 SCV005329532 pathogenic Hereditary spastic paraplegia 5A 2023-05-20 criteria provided, single submitter clinical testing The observed stop gained c.1162C>T(p.Arg388Ter) variant in CYP7B1 gene has been reported previously in homozygous state in multiple individuals affected with hereditary spastic paraplegia (Schüle R, et al., 2010; Tsaousidou MK, et al., 2008; Siam A, et al., 2012). Functional studies demonstrate that this variant leads to protein truncation and is expected to produce a non-functional gene product (Siam A, et al., 2012). The c.1162C>T variant has been reported with allele frequency of 0.0004% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Pathogenic (multiple submissions). Computational evidence (MutationTaster - Disease causing) predicts a damaging effect on protein structure and function for this variant. The nucleotide change c.1162C>T in CYP7B1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal (p.Arg388Ter) in the CYP7B1 gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in CYP7B1 gene have been previously reported to be pathogenic (Goizet C, et al., 2009). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000006473 SCV000026656 pathogenic Congenital bile acid synthesis defect 3 2008-02-01 no assertion criteria provided literature only
OMIM RCV000006474 SCV000026657 pathogenic Hereditary spastic paraplegia 5A 2008-02-01 no assertion criteria provided literature only

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