1-155239569-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

Parkinson disease
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Gaucher disease
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health, ClinGen
Gaucher disease perinatal lethal
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, Genomics England PanelApp
late-onset Parkinson disease
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
Gaucher disease type I
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
Gaucher disease type II
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
Gaucher disease type III
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

GBA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000157.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GBA1	NM_000157.4	MANE Select	c.454+47G>A	intron	N/A	NP_000148.2
GBA1	NM_001005741.3		c.454+47G>A	intron	N/A	NP_001005741.1
GBA1	NM_001005742.3		c.454+47G>A	intron	N/A	NP_001005742.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GBA1	ENST00000368373.8	TSL:1 MANE Select	c.454+47G>A	intron	N/A	ENSP00000357357.3
GBA1	ENST00000327247.9	TSL:1	c.454+47G>A	intron	N/A	ENSP00000314508.5
GBA1	ENST00000948997.1		c.454+47G>A	intron	N/A	ENSP00000619056.1

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

GnomAD2 exomes

AF:

0.367

AC:

90926

AN:

247432

AF XY:

0.357

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 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

African (AFR)

AF:

0.623

AC:

20772

AN:

33324

American (AMR)

AF:

0.401

AC:

17812

AN:

44428

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

7878

AN:

26092

East Asian (EAS)

AF:

0.727

AC:

28802

AN:

39636

South Asian (SAS)

AF:

0.345

AC:

29667

AN:

85956

European-Finnish (FIN)

AF:

0.312

AC:

16661

AN:

53348

Middle Eastern (MID)

AF:

0.234

AC:

1327

AN:

5676

European-Non Finnish (NFE)

AF:

0.292

AC:

323738

AN:

1108004

Other (OTH)

AF:

0.342

AC:

20553

AN:

60148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

16676

33351

50027

66702

83378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11162

22324

33486

44648

55810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.409

AC:

62091

AN:

151938

Hom.:

14392

Cov.:

AF XY:

0.406

AC XY:

30186

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.617

AC:

25551

AN:

41422

American (AMR)

AF:

0.360

AC:

5507

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1024

AN:

3470

East Asian (EAS)

AF:

0.704

AC:

3628

AN:

5154

South Asian (SAS)

AF:

0.356

AC:

1715

AN:

4812

European-Finnish (FIN)

AF:

0.326

AC:

3445

AN:

10558

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.297

AC:

20209

AN:

67930

Other (OTH)

AF:

0.381

AC:

804

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1730

3459

5189

6918

8648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.352

Hom.:

6539

Bravo

AF:

0.425

Asia WGS

AF:

0.563

AC:

1960

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Gaucher disease perinatal lethal (1)

Gaucher disease type I (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.086

(source)

DANN

Benign

0.62

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over