dbSNP rs998207: GBE1:c.314-2146G>A (chr3-81673099-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000158.4(GBE1):c.314-2146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 151,796 control chromosomes in the GnomAD database, including 1,148 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.085 ( 1148 hom., cov: 32)

Consequence

GBE1
NM_000158.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.777

Publications

0 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBE1	NM_000158.4 link	c.314-2146G>A		intron_variant	Intron 2 of 15	ENST00000429644.7	NP_000149.4	Q04446Q59ET0
GBE1	XR_007095662.1 link	n.442-2146G>A		intron_variant	Intron 2 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7 link	c.314-2146G>A		intron_variant	Intron 2 of 15	1	NM_000158.4	ENSP00000410833.2		Q04446
GBE1	ENST00000489715.1 link	c.191-2146G>A		intron_variant	Intron 2 of 15	2		ENSP00000419638.1		E9PGM4

Frequencies

GnomAD3 genomes

AF:

0.0853

AC:

12931

AN:

151678

Hom.:

1149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0770

Gnomad ASJ

AF:

0.0274

Gnomad EAS

AF:

0.0742

Gnomad SAS

AF:

0.0361

Gnomad FIN

AF:

0.00576

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0239

Gnomad OTH

AF:

0.0764

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0852

AC:

12937

AN:

151796

Hom.:

1148

Cov.:

AF XY:

0.0833

AC XY:

6188

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.223

AC:

9236

AN:

41424

American (AMR)

AF:

0.0768

AC:

1169

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

AN:

3462

East Asian (EAS)

AF:

0.0740

AC:

383

AN:

5178

South Asian (SAS)

AF:

0.0359

AC:

173

AN:

4816

European-Finnish (FIN)

AF:

0.00576

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0239

AC:

1621

AN:

67794

Other (OTH)

AF:

0.0765

AC:

161

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

521

1042

1562

2083

2604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0632

Hom.:

Bravo

AF:

0.0964

Asia WGS

AF:

0.0630

AC:

218

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.44

(source)

DANN

Benign

0.50

PhyloP100

-0.78

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over