rs820273

Positions:

• chr3-81498815-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000429644.7(GBE1):​c.2052+295T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,068 control chromosomes in the GnomAD database, including 11,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (11435 hom., cov: 32)
• Consequence: GBE1 ENST00000429644.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-81498815-A-G is Benign according to our data. Variant chr3-81498815-A-G is described in ClinVar as [Benign]. Clinvar id is 1178473.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBE1	NM_000158.4	c.2052+295T>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.2052+295T>C		intron_variant		1	NM_000158.4	ENSP00000410833	P1
GBE1	ENST00000489715.1	c.1929+295T>C		intron_variant		2		ENSP00000419638

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55409 AN: 151950 Hom.: 11429 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.0859

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.364 AC: 55427 AN: 152068 Hom.: 11435 Cov.: 32 AF XY: 0.365 AC XY: 27132 AN XY: 74338

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.407

Alfa AF: 0.399 Hom.: 2078

Bravo AF: 0.352

Asia WGS AF: 0.303 AC: 1051 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.73
DANN	Benign	0.86

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: rs820273; hg19: chr3-81547966;