rs17019144

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000158.4(GBE1):c.579G>A(p.Lys193Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,584,236 control chromosomes in the GnomAD database, including 3,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 1200 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1945 hom. )

Consequence

GBE1
NM_000158.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.40

Publications

7 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Laboratory for Molecular Medicine, Ambry Genetics, G2P, ClinGen
adult polyglucosan body disease
Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

GBE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 3-81648968-C-T is Benign according to our data. Variant chr3-81648968-C-T is described in ClinVar as Benign. ClinVar VariationId is 255390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBE1	NM_000158.4 link	c.579G>A	p.Lys193Lys	synonymous_variant	Exon 5 of 16	ENST00000429644.7	NP_000149.4
GBE1	XR_007095662.1 link	n.707G>A		non_coding_transcript_exon_variant	Exon 5 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
GBE1	ENST00000429644.7 link	c.579G>A	p.Lys193Lys	synonymous_variant	Exon 5 of 16	1	NM_000158.4	ENSP00000410833.2
GBE1	ENST00000489715.1 link	c.456G>A	p.Lys152Lys	synonymous_variant	Exon 5 of 16	2		ENSP00000419638.1
GBE1	ENST00000486920.1 link	n.575G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 2	3
GBE1	ENST00000498468.1 link	n.107G>A		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0893

AC:

13571

AN:

151992

Hom.:

1199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0822

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.0736

Gnomad SAS

AF:

0.0527

Gnomad FIN

AF:

0.00811

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0286

Gnomad OTH

AF:

0.0774

GnomAD2 exomes

AF:

0.0467

AC:

10447

AN:

223806

AF XY:

0.0434

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.0613

Gnomad ASJ exome

AF:

0.0271

Gnomad EAS exome

AF:

0.0595

Gnomad FIN exome

AF:

0.00570

Gnomad NFE exome

AF:

0.0255

Gnomad OTH exome

AF:

0.0386

GnomAD4 exome

AF:

0.0368

AC:

52651

AN:

1432126

Hom.:

1945

Cov.:

AF XY:

0.0367

AC XY:

26118

AN XY:

711414

show subpopulations

African (AFR)

AF:

0.225

AC:

7195

AN:

31986

American (AMR)

AF:

0.0641

AC:

2683

AN:

41838

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

728

AN:

25710

East Asian (EAS)

AF:

0.0865

AC:

3373

AN:

38996

South Asian (SAS)

AF:

0.0550

AC:

4429

AN:

80584

European-Finnish (FIN)

AF:

0.00797

AC:

418

AN:

52470

Middle Eastern (MID)

AF:

0.0691

AC:

394

AN:

5706

European-Non Finnish (NFE)

AF:

0.0280

AC:

30639

AN:

1095488

Other (OTH)

AF:

0.0470

AC:

2792

AN:

59348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

1993

3986

5979

7972

9965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1358

2716

4074

5432

6790

<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:

0.0893

AC:

13584

AN:

152110

Hom.:

1200

Cov.:

AF XY:

0.0875

AC XY:

6509

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.225

AC:

9352

AN:

41498

American (AMR)

AF:

0.0820

AC:

1253

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

AN:

3470

East Asian (EAS)

AF:

0.0734

AC:

381

AN:

5192

South Asian (SAS)

AF:

0.0525

AC:

253

AN:

4818

European-Finnish (FIN)

AF:

0.00811

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0286

AC:

1942

AN:

67928

Other (OTH)

AF:

0.0776

AC:

164

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

580

1161

1741

2322

2902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0441

Hom.:

462

Bravo

AF:

0.0997

Asia WGS

AF:

0.0680

AC:

236

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 17, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Glycogen storage disease, type IV

Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 23, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Adult polyglucosan body disease

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glycogen storage disease, type IV;C1856301:Glycogen storage disease IV, classic hepatic

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

8.1

(source)

DANN

Benign

0.65

PhyloP100

1.4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over