rs7622741

Positions:

• chr3-81501164-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000158.4(GBE1):​c.1935-1937T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,110 control chromosomes in the GnomAD database, including 7,158 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 0.30 (7158 hom., cov: 32)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBE1	NM_000158.4	c.1935-1937T>C		intron_variant		ENST00000429644.7	NP_000149.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.1935-1937T>C		intron_variant		1	NM_000158.4	ENSP00000410833	P1
GBE1	ENST00000489715.1	c.1812-1937T>C		intron_variant		2		ENSP00000419638

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45736 AN: 151992 Hom.: 7152 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.301 AC: 45784 AN: 152110 Hom.: 7158 Cov.: 32 AF XY: 0.296 AC XY: 22029 AN XY: 74376

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.289

Alfa AF: 0.272 Hom.: 12807

Bravo AF: 0.313

Asia WGS AF: 0.292 AC: 1016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs7622741; hg19: chr3-81550315;