chr3-81673099-C-T

Variant names:

• chr3-81673099-C-T
• rs998207
• NM_000158.4:c.314-2146G>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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777
• Publications: 0 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBE1	NM_000158.4	MANE Select	c.314-2146G>A		intron	N/A	NP_000149.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBE1	ENST00000429644.7	TSL:1 MANE Select	c.314-2146G>A		intron	N/A	ENSP00000410833.2
	GBE1	ENST00000489715.1	TSL:2	c.191-2146G>A		intron	N/A	ENSP00000419638.1

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12931 AN: 151678 Hom.: 1149 Cov.: 32

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.: 32 AF XY: 0.0833 AC XY: 6188 AN XY: 74246

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: 95 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: 61 AN: 10592

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0239 AC: 1621 AN: 67794

Other (OTH) AF: 0.0765 AC: 161 AN: 2104

Alfa AF: 0.0632 Hom.: 97

Bravo AF: 0.0964

Asia WGS AF: 0.0630 AC: 218 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.50
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs998207; hg19: chr3-81722250;