rs2229519

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000158.4(GBE1):c.568A>G(p.Arg190Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,571,242 control chromosomes in the GnomAD database, including 75,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6997 hom., cov: 32)

Exomes 𝑓: 0.31 ( 68475 hom. )

Consequence

GBE1
NM_000158.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:19

Conservation

PhyloP100: 3.51

Publications

44 publications found

Variant links:

Genes affected

GBE1 (HGNC:4180): (1,4-alpha-glucan branching enzyme 1) The protein encoded by this gene is a glycogen branching enzyme that catalyzes the transfer of alpha-1,4-linked glucosyl units from the outer end of a glycogen chain to an alpha-1,6 position on the same or a neighboring glycogen chain. Branching of the chains is essential to increase the solubility of the glycogen molecule and, consequently, in reducing the osmotic pressure within cells. Highest level of this enzyme are found in liver and muscle. Mutations in this gene are associated with glycogen storage disease IV (also known as Andersen's disease). [provided by RefSeq, Jul 2008]

GBE1 Gene-Disease associations (from GenCC):

glycogen storage disease due to glycogen branching enzyme deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
adult polyglucosan body disease
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

GBE1 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 (MetaRNN=0.002937764).

BP6

Variant 3-81648979-T-C is Benign according to our data. Variant chr3-81648979-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 197636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000158.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBE1	NM_000158.4	MANE Select	c.568A>G	p.Arg190Gly	missense	Exon 5 of 16	NP_000149.4	Q04446

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GBE1	ENST00000429644.7	TSL:1 MANE Select	c.568A>G	p.Arg190Gly	missense	Exon 5 of 16	ENSP00000410833.2	Q04446
GBE1	ENST00000895874.1		c.568A>G	p.Arg190Gly	missense	Exon 5 of 16	ENSP00000565933.1
GBE1	ENST00000942742.1		c.562A>G	p.Arg188Gly	missense	Exon 5 of 16	ENSP00000612801.1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45374

AN:

151906

Hom.:

6994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.270

GnomAD2 exomes

AF:

0.317

AC:

70584

AN:

222350

AF XY:

0.316

show subpopulations

Gnomad AFR exome

AF:

0.278

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.452

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.305

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.306

AC:

434420

AN:

1419218

Hom.:

68475

Cov.:

AF XY:

0.305

AC XY:

215363

AN XY:

705024

show subpopulations

African (AFR)

AF:

0.275

AC:

8798

AN:

31946

American (AMR)

AF:

0.292

AC:

12046

AN:

41306

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

5287

AN:

25606

East Asian (EAS)

AF:

0.432

AC:

16756

AN:

38784

South Asian (SAS)

AF:

0.296

AC:

23806

AN:

80334

European-Finnish (FIN)

AF:

0.414

AC:

21522

AN:

52018

Middle Eastern (MID)

AF:

0.210

AC:

1196

AN:

5690

European-Non Finnish (NFE)

AF:

0.302

AC:

327313

AN:

1084656

Other (OTH)

AF:

0.301

AC:

17696

AN:

58878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

11814

23628

35443

47257

59071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10750

21500

32250

43000

53750

<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:

0.299

AC:

45395

AN:

152024

Hom.:

6997

Cov.:

AF XY:

0.303

AC XY:

22480

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.274

AC:

11370

AN:

41500

American (AMR)

AF:

0.259

AC:

3960

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

715

AN:

3468

East Asian (EAS)

AF:

0.444

AC:

2298

AN:

5174

South Asian (SAS)

AF:

0.311

AC:

1500

AN:

4818

European-Finnish (FIN)

AF:

0.402

AC:

4244

AN:

10552

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.302

AC:

20489

AN:

67904

Other (OTH)

AF:

0.271

AC:

572

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1622

3243

4865

6486

8108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<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:

0.299

Hom.:

28517

Bravo

AF:

0.290

TwinsUK

AF:

0.309

AC:

1144

ALSPAC

AF:

0.304

AC:

1170

ESP6500AA

AF:

0.277

AC:

992

ESP6500EA

AF:

0.301

AC:

2441

ExAC

AF:

0.306

AC:

36856

Asia WGS

AF:

0.391

AC:

1360

AN:

3472

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (8)

Glycogen storage disease, type IV (5)

Adult polyglucosan body disease (3)

not provided (2)

Glycogen storage disease, type IV;C1856301:Glycogen storage disease IV, classic hepatic (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.71

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

PhyloP100

3.5

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.32

Sift

Uncertain

0.020

Sift4G

Benign

0.066

Polyphen

0.013

Vest4

0.089

MPC

0.041

ClinPred

0.056

GERP RS

4.8

Varity_R

0.37

gMVP

0.68

Mutation Taster

=96/4

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