NM_000157.4(GBA1):c.1604G>A (p.Arg535His) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Jan 11, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000790684.27

Allele description [Variation Report for NM_000157.4(GBA1):c.1604G>A (p.Arg535His)]

NM_000157.4(GBA1):c.1604G>A (p.Arg535His)

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.1604G>A (p.Arg535His)

Other names:

R496H

HGVS:

NC_000001.11:g.155235002C>T
NG_009783.1:g.14696G>A
NG_042867.1:g.1464C>T
NM_000157.3(GBA):c.1604G>A
NM_000157.4:c.1604G>AMANE SELECT
NM_001005741.3:c.1604G>A
NM_001005742.3:c.1604G>A
NM_001171811.2:c.1343G>A
NM_001171812.2:c.1457G>A
NP_000148.2:p.Arg535His
NP_001005741.1:p.Arg535His
NP_001005742.1:p.Arg535His
NP_001165282.1:p.Arg448His
NP_001165283.1:p.Arg486His
NC_000001.10:g.155204793C>T
NM_000157.2:c.1604G>A
NM_000157.3(GBA):c.1604G>A
NM_000157.3:c.1604G>A
NM_000157.4:c.1604G>A
NM_001005741.2:c.1604G>A
NM_001005741.3:c.1604G>A
NM_001005742.2:c.1604G>A
P04062:p.Arg535His
c.1604G>A (p.Arg535His)

Protein change:

R448H; ARG496HIS

Links:

UniProtKB: P04062#VAR_003328; OMIM: 606463.0022; dbSNP: rs75822236

NCBI 1000 Genomes Browser:

rs75822236

Molecular consequence:

NM_000157.4:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005741.3:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005742.3:c.1604G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171811.2:c.1343G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171812.2:c.1457G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000225538	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Apr 27, 2015)	germline	clinical testing	Citation Link,
SCV000930789	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 11, 2024)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 8432537, 12972024, 23430543, 23588557, 23699752, 25933391, 27735925, 16293621, 28492532
SCV001803479	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 11, 2019)	germline	clinical testing	Citation Link,
SCV002024199	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 23, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002502715	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 10, 2021)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 8432537, 23699752, 22975760, 16293621, 23588557, 29842932, 28966932, 27735925, 32042592, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	3	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The 1604A (R496H) mutation in Gaucher disease: genotype/phenotype correlation.

Brautbar A, Elstein D, Abrahamov A, Zeigler M, Chicco G, Beutler E, Scott CR, Zimran A.

Blood Cells Mol Dis. 2003 Sep-Oct;31(2):187-9; discussion 190-1.

PubMed [citation]

PMID:: 12972024

Novel mutations in the glucocerebrosidase gene of brazilian patients with Gaucher disease.

Siebert M, Bock H, Michelin-Tirelli K, Coelho JC, Giugliani R, Saraiva-Pereira ML.

JIMD Rep. 2013;9:7-16. doi: 10.1007/8904_2012_174. Epub 2012 Oct 9.

PubMed [citation]

PMID:: 23430543
PMCID:: PMC3565676

See all PubMed Citations (14)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000225538.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

#	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		3	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000930789.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 535 of the GBA protein (p.Arg535His). This variant is present in population databases (rs75822236, gnomAD 0.2%). This missense change has been observed in individual(s) with dementia with Lewy bodies, Gaucher disease, and/or Parkinson's disease (PMID: 8432537, 12972024, 23430543, 23588557, 23699752, 25933391, 27735925). This variant is also known as p.Arg496His or R496H. ClinVar contains an entry for this variant (Variation ID: 4311). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GBA protein function. Experimental studies have shown that this missense change affects GBA function (PMID: 16293621). For these reasons, this variant has been classified as Pathogenic.

#	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

From GeneDx, SCV001803479.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate that this variant had little or no catalytic activity (Liou et al., 2006); This variant is associated with the following publications: (PMID: 33176831, 29471591, 31589614, 32985097, 32042592, 28966932, 29842932, 27735925, 23430543, 12972024, 8432537, 18434642, 26233692, 26857292, 16148263, 22935721, 16293621, 22975760, 23699752, 23588557)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002024199.3

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

#	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

From AiLife Diagnostics, AiLife Diagnostics, SCV002502715.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (10)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine