U.S. flag

An official website of the United States government

NM_000071.3(CBS):c.532-1G>A AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 30, 2021
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:
RCV001931836.4

Allele description [Variation Report for NM_000071.3(CBS):c.532-1G>A]

NM_000071.3(CBS):c.532-1G>A

Gene:
CBS:cystathionine beta-synthase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.3
Genomic location:
Preferred name:
NM_000071.3(CBS):c.532-1G>A
HGVS:
  • NC_000021.9:g.43065522C>T
  • NG_008938.1:g.15409G>A
  • NM_000071.3:c.532-1G>AMANE SELECT
  • NM_001178008.3:c.532-1G>A
  • NM_001178009.3:c.532-1G>A
  • NM_001320298.2:c.532-1G>A
  • NM_001321072.1:c.217-1G>A
  • LRG_777:g.15409G>A
  • NC_000021.8:g.44485632C>T
Links:
dbSNP: rs2146385603
NCBI 1000 Genomes Browser:
rs2146385603
Molecular consequence:
  • NM_000071.3:c.532-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001178008.3:c.532-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001178009.3:c.532-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001320298.2:c.532-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001321072.1:c.217-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
Identifiers:
MedGen: C3150344

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002123695Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 30, 2021) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Cystathionine beta-synthase mutations in homocystinuria.

Kraus JP, Janosík M, Kozich V, Mandell R, Shih V, Sperandeo MP, Sebastio G, de Franchis R, Andria G, Kluijtmans LA, Blom H, Boers GH, Gordon RB, Kamoun P, Tsai MY, Kruger WD, Koch HG, Ohura T, Gaustadnes M.

Hum Mutat. 1999;13(5):362-75. Review.

PubMed [citation]
PMID:
10338090
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002123695.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with clinical features of CBS deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the CBS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CBS are known to be pathogenic (PMID: 10338090, 12124992).

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

Last Updated: Sep 29, 2024