Variant rs147411159 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_000157.4(GBA1):c.474C>T(p.Ile158Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000635 in 1,613,718 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00051 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00065 ( 1 hom. )

Consequence

GBA1
NM_000157.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 0.447

Variant links:

Genes affected

GBA1 (HGNC:4177): (glucosylceramidase beta 1) This gene encodes a lysosomal membrane protein that cleaves the beta-glucosidic linkage of glycosylceramide, an intermediate in glycolipid metabolism. Mutations in this gene cause Gaucher disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides. A related pseudogene is approximately 12 kb downstream of this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2010]

GBA1 links:

GBA1 (HGNC:):

GBA1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 1-155238631-G-A is Benign according to our data. Variant chr1-155238631-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 225285.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chr1-155238631-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.447 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBA1	NM_000157.4 linkuse as main transcript	c.474C>T	p.Ile158Ile	synonymous_variant	5/11	ENST00000368373.8	NP_000148.2	P04062-1A0A068F658

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBA1	ENST00000368373.8 linkuse as main transcript	c.474C>T	p.Ile158Ile	synonymous_variant	5/11	1	NM_000157.4	ENSP00000357357.3		P04062-1

Frequencies

GnomAD3 genomes

AF:

0.000507

AC:

AN:

151942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000677

AC:

170

AN:

251182

Hom.:

AF XY:

0.000700

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000649

AC:

948

AN:

1461658

Hom.:

Cov.:

AF XY:

0.000638

AC XY:

464

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.000764

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000506

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000982

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000650

Hom.:

Bravo

AF:

0.000484

EpiCase

AF:

0.000927

EpiControl

AF:

0.000771

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Gaucher disease

Uncertain:1Benign:1

Likely benign, no assertion criteria provided	clinical testing	Natera, Inc.	Jun 02, 2020	- -
Uncertain significance, criteria provided, single submitter	research	CSER _CC_NCGL, University of Washington	Jan 01, 2016	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	GBA1: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2021	This variant is associated with the following publications: (PMID: 25637381) -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

May 03, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.4

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over