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NM_000158.4(GBE1):c.783-1G>A AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 18, 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:
RCV003764518.2

Allele description [Variation Report for NM_000158.4(GBE1):c.783-1G>A]

NM_000158.4(GBE1):c.783-1G>A

Gene:
GBE1:1,4-alpha-glucan branching enzyme 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p12.2
Genomic location:
Preferred name:
NM_000158.4(GBE1):c.783-1G>A
HGVS:
  • NC_000003.12:g.81642991C>T
  • NG_011810.1:g.123810G>A
  • NG_011810.2:g.123654G>A
  • NM_000158.4:c.783-1G>AMANE SELECT
  • NC_000003.11:g.81692142C>T
  • NM_000158.3:c.783-1G>A
Nucleotide change:
IVSAS, G-A, -1
Links:
OMIM: 607839.0001; dbSNP: rs397515342
NCBI 1000 Genomes Browser:
rs397515342
Molecular consequence:
  • NM_000158.4:c.783-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Glycogen storage disease, type IV (GSD4)
Synonyms:
GBE1 DEFICIENCY; GLYCOGENOSIS IV; GSD IV; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009292; MedGen: C0017923; Orphanet: 367; OMIM: 232500
Name:
Glycogen storage disease IV, classic hepatic
Synonyms:
GSD IV, CLASSIC HEPATIC
Identifiers:
MedGen: C1856301

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004569657Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Oct 18, 2022) 		germlineclinical testing

PubMed (2)
[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

Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene.

Bao Y, Kishnani P, Wu JY, Chen YT.

J Clin Invest. 1996 Feb 15;97(4):941-8.

PubMed [citation]
PMID:
8613547
PMCID:
PMC507139

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, SCV004569657.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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 skipping of exon 7, but is expected to preserve the integrity of the reading-frame (PMID: 8613547). Experimental studies have shown that disruption of this splice site affects GBE1 function (PMID: 8613547). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 2776). This variant is also known as a 210-bp deletion from nucleotide 873 to 1082 due to a g-to-a substitution at the 3' end of the intron. Disruption of this splice site has been observed in individual(s) with glycogen storage disease (PMID: 8613547). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the GBE1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product.

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

Last Updated: Sep 29, 2024