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NM_000157.4(GBA1):c.1444G>A (p.Asp482Asn) AND not specified

Germline classification:
Likely benign (1 submission)
Last evaluated:
Jan 6, 2020
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:
RCV001174737.1

Allele description [Variation Report for NM_000157.4(GBA1):c.1444G>A (p.Asp482Asn)]

NM_000157.4(GBA1):c.1444G>A (p.Asp482Asn)

Genes:
LOC106627981:GBA recombination region [Gene]
GBA1:glucosylceramidase beta 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q22
Genomic location:
Preferred name:
NM_000157.4(GBA1):c.1444G>A (p.Asp482Asn)
Other names:
D443N
HGVS:
  • NC_000001.11:g.155235256C>T
  • NG_009783.1:g.14442G>A
  • NG_042867.1:g.1718C>T
  • NM_000157.4:c.1444G>AMANE SELECT
  • NM_001005741.3:c.1444G>A
  • NM_001005742.3:c.1444G>A
  • NM_001171811.2:c.1183G>A
  • NM_001171812.2:c.1297G>A
  • NP_000148.2:p.Asp482Asn
  • NP_001005741.1:p.Asp482Asn
  • NP_001005742.1:p.Asp482Asn
  • NP_001165282.1:p.Asp395Asn
  • NP_001165283.1:p.Asp433Asn
  • NC_000001.10:g.155205047C>T
  • NM_000157.4:c.1444G>A
  • NM_001005741.2:c.1444G>A
  • P04062:p.Asp482Asn
Protein change:
D395N; ASP443ASN
Links:
UniProtKB: P04062#VAR_063067; OMIM: 606463.0048; dbSNP: rs75671029
NCBI 1000 Genomes Browser:
rs75671029
Molecular consequence:
  • NM_000157.4:c.1444G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005741.3:c.1444G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005742.3:c.1444G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171811.2:c.1183G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171812.2:c.1297G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001338026Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Jan 6, 2020) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Glucocerebrosidase mutations in primary parkinsonism.

Asselta R, Rimoldi V, Siri C, Cilia R, Guella I, Tesei S, Soldà G, Pezzoli G, Duga S, Goldwurm S.

Parkinsonism Relat Disord. 2014 Nov;20(11):1215-20. doi: 10.1016/j.parkreldis.2014.09.003. Epub 2014 Sep 9.

PubMed [citation]
PMID:
25249066
PMCID:
PMC4228056

GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease.

Mata IF, Leverenz JB, Weintraub D, Trojanowski JQ, Chen-Plotkin A, Van Deerlin VM, Ritz B, Rausch R, Factor SA, Wood-Siverio C, Quinn JF, Chung KA, Peterson-Hiller AL, Goldman JG, Stebbins GT, Bernard B, Espay AJ, Revilla FJ, Devoto J, Rosenthal LS, Dawson TM, Albert MS, et al.

Mov Disord. 2016 Jan;31(1):95-102. doi: 10.1002/mds.26359. Epub 2015 Aug 21.

PubMed [citation]
PMID:
26296077
PMCID:
PMC4724255
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001338026.1

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

Description

Variant summary: GBA c.1444G>A (p.Asp482Asn) results in a conservative amino acid change located in the Glycosyl hydrolase family 30, beta sandwich domain (IPR033452) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00052 in 253860 control chromosomes, predominantly at a frequency of 0.0075 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in GBA causing Gaucher Disease phenotype (0.005), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1444G>A has been reported in the literature in individuals affected with Parkinson's disease (e.g. Asselta_2014, Gan-Or_2015, Neumann_2009). These reports however, do not provide unequivocal conclusions about association of the variant with Gaucher Disease. It was reported in the literature that GBA mutations may be a risk factor for Parkinson's disease (e.g. PMIDs: 19502295, 26860875). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Oct 20, 2024