NM_004820.5(CYP7B1):c.1457G>A (p.Arg486His) AND Spastic paraplegia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 9, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001235957.5

Allele description [Variation Report for NM_004820.5(CYP7B1):c.1457G>A (p.Arg486His)]

NM_004820.5(CYP7B1):c.1457G>A (p.Arg486His)

Gene:

CYP7B1:cytochrome P450 family 7 subfamily B member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q12.3

Genomic location:

Preferred name:

NM_004820.5(CYP7B1):c.1457G>A (p.Arg486His)

HGVS:

NC_000008.11:g.64596706C>T
NG_008338.2:g.207086G>A
NM_001324112.2:c.1234-6862G>A
NM_004820.5:c.1457G>AMANE SELECT
NP_004811.1:p.Arg486His
NC_000008.10:g.65509263C>T
NM_004820.3:c.1457G>A

Protein change:

R486H

Links:

dbSNP: rs755729966

NCBI 1000 Genomes Browser:

rs755729966

Molecular consequence:

NM_001324112.2:c.1234-6862G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_004820.5:c.1457G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spastic paraplegia
Identifiers:: MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001408666	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19439420, 21623769, 23812641, 24117163, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001408666

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 9, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5.

Goizet C, Boukhris A, Durr A, Beetz C, Truchetto J, Tesson C, Tsaousidou M, Forlani S, Guyant-Maréchal L, Fontaine B, Guimarães J, Isidor B, Chazouillères O, Wendum D, Grid D, Chevy F, Chinnery PF, Coutinho P, Azulay JP, Feki I, Mochel F, Wolf C, et al.

Brain. 2009 Jun;132(Pt 6):1589-600. doi: 10.1093/brain/awp073. Epub 2009 May 12.

PubMed [citation]

PMID:: 19439420

Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients.

Schlipf NA, Schüle R, Klimpe S, Karle KN, Synofzik M, Schicks J, Riess O, Schöls L, Bauer P.

Clin Genet. 2011 Aug;80(2):148-60. doi: 10.1111/j.1399-0004.2011.01715.x. Epub 2011 Jun 13.

PubMed [citation]

PMID:: 21623769

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001408666.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 486 of the CYP7B1 protein (p.Arg486His). This variant is present in population databases (rs755729966, gnomAD 0.02%). 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: 962151). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg486 amino acid residue in CYP7B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19439420, 21623769, 23812641, 24117163). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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