3-81489477-C-T

Variant names:

• chr3-81489477-C-T
• rs9815059
• NM_000158.4:c.*930G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000158.4(GBE1):​c.*930G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,744 control chromosomes in the GnomAD database, including 6,775 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 0.29 (6775 hom., cov: 32)
• Consequence: GBE1 NM_000158.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBE1	NM_000158.4	c.*930G>A		downstream_gene_variant		ENST00000429644.7	NP_000149.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.*930G>A		downstream_gene_variant		1	NM_000158.4	ENSP00000410833.2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44628 AN: 151626 Hom.: 6770 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.294 AC: 44676 AN: 151744 Hom.: 6775 Cov.: 32 AF XY: 0.291 AC XY: 21561 AN XY: 74146

African (AFR) AF: 0.360 AC: 14890 AN: 41400

American (AMR) AF: 0.269 AC: 4095 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3466

East Asian (EAS) AF: 0.427 AC: 2200 AN: 5154

South Asian (SAS) AF: 0.164 AC: 790 AN: 4820

European-Finnish (FIN) AF: 0.250 AC: 2626 AN: 10504

Middle Eastern (MID) AF: 0.262 AC: 76 AN: 290

European-Non Finnish (NFE) AF: 0.274 AC: 18600 AN: 67858

Other (OTH) AF: 0.278 AC: 584 AN: 2104

Alfa AF: 0.282 Hom.: 1273

Bravo AF: 0.303

Asia WGS AF: 0.291 AC: 1007 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.43
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs9815059; hg19: chr3-81538628;