rs9628662

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000157.4(GBA1):c.1000-81A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,142,664 control chromosomes in the GnomAD database, including 69,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 12483 hom., cov: 31)

Exomes 𝑓: 0.32 ( 57135 hom. )

Consequence

GBA1
NM_000157.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.292

Publications

34 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: Genomics England PanelApp, Laboratory for Molecular Medicine, G2P
late-onset Parkinson disease
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
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: Genomics England PanelApp, Orphanet
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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-155236550-T-G is Benign according to our data. Variant chr1-155236550-T-G is described in ClinVar as Benign. ClinVar VariationId is 828082.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 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	UniProt
GBA1	NM_000157.4	MANE Select	c.1000-81A>C	intron	N/A	NP_000148.2	P04062-1
GBA1	NM_001005741.3		c.1000-81A>C	intron	N/A	NP_001005741.1	P04062-1
GBA1	NM_001005742.3		c.1000-81A>C	intron	N/A	NP_001005742.1	P04062-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GBA1	ENST00000368373.8	TSL:1 MANE Select	c.1000-81A>C	intron	N/A	ENSP00000357357.3	P04062-1
GBA1	ENST00000327247.9	TSL:1	c.1000-81A>C	intron	N/A	ENSP00000314508.5	P04062-1
GBA1	ENST00000948997.1		c.1066-81A>C	intron	N/A	ENSP00000619056.1

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58841

AN:

151774

Hom.:

12448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.366

GnomAD4 exome

AF:

0.322

AC:

319472

AN:

990772

Hom.:

57135

AF XY:

0.321

AC XY:

163314

AN XY:

508656

show subpopulations

African (AFR)

AF:

0.543

AC:

12965

AN:

23888

American (AMR)

AF:

0.393

AC:

14592

AN:

37164

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

6826

AN:

22714

East Asian (EAS)

AF:

0.730

AC:

26135

AN:

35798

South Asian (SAS)

AF:

0.341

AC:

24968

AN:

73134

European-Finnish (FIN)

AF:

0.314

AC:

15779

AN:

50268

Middle Eastern (MID)

AF:

0.225

AC:

1114

AN:

4946

European-Non Finnish (NFE)

AF:

0.289

AC:

202034

AN:

697930

Other (OTH)

AF:

0.335

AC:

15059

AN:

44930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

12248

24496

36745

48993

61241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5564

11128

16692

22256

27820

<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:

0.388

AC:

58918

AN:

151892

Hom.:

12483

Cov.:

AF XY:

0.388

AC XY:

28776

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.539

AC:

22309

AN:

41380

American (AMR)

AF:

0.353

AC:

5385

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1023

AN:

3464

East Asian (EAS)

AF:

0.705

AC:

3646

AN:

5174

South Asian (SAS)

AF:

0.356

AC:

1716

AN:

4818

European-Finnish (FIN)

AF:

0.327

AC:

3452

AN:

10546

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.301

AC:

20415

AN:

67926

Other (OTH)

AF:

0.363

AC:

767

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1769

3538

5308

7077

8846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.326

Hom.:

14221

Bravo

AF:

0.401

Asia WGS

AF:

0.555

AC:

1930

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Gaucher disease (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.81

(source)

DANN

Benign

0.50

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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