Variant 1-155239569-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000157.4(GBA1):c.454+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,608,550 control chromosomes in the GnomAD database, including 95,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14392 hom., cov: 31)

Exomes 𝑓: 0.32 ( 81167 hom. )

Consequence

GBA1
NM_000157.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.42

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 1-155239569-C-T is Benign according to our data. Variant chr1-155239569-C-T is described in ClinVar as [Benign]. Clinvar id is 256873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBA1	NM_000157.4 link	c.454+47G>A		intron_variant		ENST00000368373.8	NP_000148.2	P04062-1A0A068F658

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBA1	ENST00000368373.8 link	c.454+47G>A		intron_variant		1	NM_000157.4	ENSP00000357357.3		P04062-1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61998

AN:

151820

Hom.:

14346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.616

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.384

GnomAD3 exomes

AF:

0.367

AC:

90926

AN:

247432

Hom.:

18697

AF XY:

0.357

AC XY:

47844

AN XY:

134170

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.403

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.706

Gnomad SAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.339

GnomAD4 exome

AF:

0.321

AC:

467210

AN:

1456612

Hom.:

81167

Cov.:

AF XY:

0.319

AC XY:

231011

AN XY:

724818

show subpopulations

Gnomad4 AFR exome

AF:

0.623

Gnomad4 AMR exome

AF:

0.401

Gnomad4 ASJ exome

AF:

0.302

Gnomad4 EAS exome

AF:

0.727

Gnomad4 SAS exome

AF:

0.345

Gnomad4 FIN exome

AF:

0.312

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.342

GnomAD4 genome

AF:

0.409

AC:

62091

AN:

151938

Hom.:

14392

Cov.:

AF XY:

0.406

AC XY:

30186

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.617

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.704

Gnomad4 SAS

AF:

0.356

Gnomad4 FIN

AF:

0.326

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.381

Alfa

AF:

0.329

Hom.:

3596

Bravo

AF:

0.425

Asia WGS

AF:

0.563

AC:

1960

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 31, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 54% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 50. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Gaucher disease type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Gaucher disease perinatal lethal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.086

DANN

Benign

0.62

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