NM_004820.5(CYP7B1):c.1456C>T (p.Arg486Cys) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 29, 2024
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:: RCV000197085.12

Allele description [Variation Report for NM_004820.5(CYP7B1):c.1456C>T (p.Arg486Cys)]

NM_004820.5(CYP7B1):c.1456C>T (p.Arg486Cys)

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.1456C>T (p.Arg486Cys)

HGVS:

NC_000008.11:g.64596707G>A
NG_008338.2:g.207085C>T
NM_001324112.2:c.1234-6863C>T
NM_004820.5:c.1456C>TMANE SELECT
NP_004811.1:p.Arg486Cys
NC_000008.10:g.65509264G>A
NM_004820.3:c.1456C>T
NM_004820.4:c.1456C>T
O75881:p.Arg486Cys

Protein change:

R486C; ARG486CYS

Links:

UniProtKB: O75881#VAR_075518; OMIM: 603711.0008; dbSNP: rs116171274

NCBI 1000 Genomes Browser:

rs116171274

Molecular consequence:

NM_001324112.2:c.1234-6863C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_004820.5:c.1456C>T - 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
SCV000253708	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 29, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 19439420, 21623769, 23812641, 24117163, 21541746, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000253708

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 29, 2024)

germline

clinical testing

PubMed (6)
[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 (6)

Details of each submission

From Invitae, SCV000253708.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 486 of the CYP7B1 protein (p.Arg486Cys). This variant is present in population databases (rs116171274, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individuals with hereditary spastic paraplegia. In these individuals, this variant was observed in either the homozygous state or compound heterozygous state (PMID: 19439420, 21623769, 23812641, 24117163). ClinVar contains an entry for this variant (Variation ID: 6107). An algorithm developed specifically for the CYP7B1 gene suggests that this missense change is likely to be deleterious (PMID: 21541746). For these reasons, this variant has been classified as Pathogenic.

#	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: Apr 15, 2024

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