chr3-81574376-A-G

Position:

• chr3-81574376-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.1618+3549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,048 control chromosomes in the GnomAD database, including 6,951 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 (6951 hom., cov: 31)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBE1	NM_000158.4	c.1618+3549T>C		intron_variant		ENST00000429644.7
GBE1	XR_007095662.1	n.1746+3549T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBE1	ENST00000429644.7	c.1618+3549T>C		intron_variant		1	NM_000158.4	P1
GBE1	ENST00000489715.1	c.1495+3549T>C		intron_variant		2
GBE1	ENST00000484687.1	n.19+3549T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45163 AN: 151930 Hom.: 6942 Cov.: 31

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.297 AC: 45218 AN: 152048 Hom.: 6951 Cov.: 31 AF XY: 0.293 AC XY: 21773 AN XY: 74334

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.284

Alfa AF: 0.292 Hom.: 1199

Bravo AF: 0.308

Asia WGS AF: 0.294 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.35

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: rs7631349; hg19: chr3-81623527;