NM_000071.3(CBS):c.210-1G>C AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 15, 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:: RCV002017343.4

Allele description [Variation Report for NM_000071.3(CBS):c.210-1G>C]

NM_000071.3(CBS):c.210-1G>C

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.210-1G>C

HGVS:

NC_000021.9:g.43068616C>G
NG_008938.1:g.12315G>C
NM_000071.3:c.210-1G>CMANE SELECT
NM_001178008.3:c.210-1G>C
NM_001178009.3:c.210-1G>C
NM_001320298.2:c.210-1G>C
LRG_777:g.12315G>C
NC_000021.8:g.44488726C>G

Links:

dbSNP: rs2146414477

NCBI 1000 Genomes Browser:

rs2146414477

Molecular consequence:

NM_000071.3:c.210-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001178008.3:c.210-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001178009.3:c.210-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001320298.2:c.210-1G>C - 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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002295682	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 15, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11359213, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002295682

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 15, 2021)

germline

clinical testing

PubMed (2)
[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

Impaired heme binding and aggregation of mutant cystathionine beta-synthase subunits in homocystinuria.

Janosík M, Oliveriusová J, Janosíková B, Sokolová J, Kraus E, Kraus JP, Kozich V.

Am J Hum Genet. 2001 Jun;68(6):1506-13. Epub 2001 May 15.

PubMed [citation]

PMID:: 11359213
PMCID:: PMC1226138

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002295682.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Studies have shown that disruption of this splice site results in a frameshift (c.210_235del26), which introduces a new termination codon (PMID: 11359213). However the mRNA is not expected to undergo nonsense-mediated decay. This variant is also known as IVS1-1G>C. Disruption of this splice site has been observed in individual(s) with homocystinuria (PMID: 11359213). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 3 of the CBS gene. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein.

#	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

ClinVar

Relating variation to medicine