rs762945205

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000158.4(GBE1):c.292G>C(p.Val98Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000609 in 1,593,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V98G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

GBE1
NM_000158.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:8

Conservation

PhyloP100: 4.79

Publications

2 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1602934).

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.292G>C	p.Val98Leu	missense	Exon 2 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.292G>C	p.Val98Leu	missense	Exon 2 of 16	ENSP00000410833.2	Q04446
GBE1	ENST00000895874.1		c.292G>C	p.Val98Leu	missense	Exon 2 of 16	ENSP00000565933.1
GBE1	ENST00000942742.1		c.292G>C	p.Val98Leu	missense	Exon 2 of 16	ENSP00000612801.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000397

AC:

AN:

226798

AF XY:

0.0000489

show subpopulations

Gnomad AFR exome

AF:

0.0000701

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000675

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.0000638

AC:

AN:

1441040

Hom.:

Cov.:

AF XY:

0.0000615

AC XY:

AN XY:

715104

show subpopulations

African (AFR)

AF:

0.0000915

AC:

AN:

32790

American (AMR)

AF:

0.00

AC:

AN:

41324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25692

East Asian (EAS)

AF:

0.00

AC:

AN:

38916

South Asian (SAS)

AF:

0.00

AC:

AN:

80742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52928

Middle Eastern (MID)

AF:

0.00332

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.0000544

AC:

AN:

1103240

Other (OTH)

AF:

0.000168

AC:

AN:

59678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000329

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000113

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000746

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease, type IV (3)

Adult polyglucosan body disease (2)

Glycogen storage disease, type IV;C1849722:Adult polyglucosan body disease (1)

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

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.17

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0093

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

4.8

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.26

REVEL

Benign

0.16

Sift

Benign

0.39

Sift4G

Benign

0.45

Polyphen

0.0030

Vest4

0.50

MVP

0.25

MPC

0.035

ClinPred

0.061

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.78

Mutation Taster

=53/47

polymorphism

(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

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