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NM_004820.5(CYP7B1):c.1250G>A (p.Arg417His) AND CYP7B1-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 27, 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:
RCV003894794.1

Allele description

NM_004820.5(CYP7B1):c.1250G>A (p.Arg417His)

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.1250G>A (p.Arg417His)
HGVS:
  • NC_000008.11:g.64596913C>T
  • NG_008338.2:g.206879G>A
  • NM_001324112.2:c.1234-7069G>A
  • NM_004820.5:c.1250G>AMANE SELECT
  • NP_004811.1:p.Arg417His
  • NC_000008.10:g.65509470C>T
  • NM_004820.3:c.1250G>A
  • NM_004820.4:c.1250G>A
  • O75881:p.Arg417His
Protein change:
R417H; ARG417HIS
Links:
UniProtKB: O75881#VAR_044385; OMIM: 603711.0004; dbSNP: rs121908611
NCBI 1000 Genomes Browser:
rs121908611
Molecular consequence:
  • NM_001324112.2:c.1234-7069G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_004820.5:c.1250G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
CYP7B1-related disorder
Synonyms:
CYP7B1-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004714941PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 27, 2024) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004714941.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The CYP7B1 c.1250G>A variant is predicted to result in the amino acid substitution p.Arg417His. This variant was reported in the homozygous state in an individual with hereditary spastic paraplegia (Family 2, Tsaousidou et al 2008. PubMed ID: 18252231). This variant was also identified in the heterozygous state, and interpreted as pathogenic, in three individuals in a study utiziling exome sequencing for preconception carrier screening (Supplementary Table 1, Capalbo A et al 2019. PubMed ID: 31589614). Comparative modeling of CYP7B1 shows that the R417 amino acid resides in the meander region, which is the conserved PERF region, and suggests that any variant involving the R417 amino acid would be predicted to severely affect enzyme function (Siam A et al 2011. PubMed ID: 21541746). In addition, other variants impact the R417 amino acids have also been reported in individuals with hereditary spastic paraplegia (Goizet et al. 2009. PubMed ID: 19439420; Cao et al. 2011. PubMed ID: 21452256). This variant is reported in 0.010% of alleles in individuals of East Asian descent in gnomAD. Taken together, we interpret this variant as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024