rs820273

Variant names:

• chr3-81498815-A-G
• rs820273
• NM_000158.4:c.2052+295T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000158.4(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 NM_000158.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10
• Publications: 2 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 -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 VariationId 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 rank	MANE	Protein	UniProt
GBE1	NM_000158.4	c.2052+295T>C		intron_variant	Intron 15 of 15	ENST00000429644.7	NP_000149.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.2052+295T>C		intron_variant	Intron 15 of 15	1	NM_000158.4	ENSP00000410833.2
GBE1	ENST00000489715.1	c.1929+295T>C		intron_variant	Intron 15 of 15	2		ENSP00000419638.1

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

African (AFR) AF: 0.185 AC: 7693 AN: 41522

American (AMR) AF: 0.419 AC: 6382 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2096 AN: 3464

East Asian (EAS) AF: 0.0859 AC: 445 AN: 5180

South Asian (SAS) AF: 0.549 AC: 2651 AN: 4826

European-Finnish (FIN) AF: 0.395 AC: 4172 AN: 10560

Middle Eastern (MID) AF: 0.476 AC: 138 AN: 290

European-Non Finnish (NFE) AF: 0.448 AC: 30443 AN: 67958

Other (OTH) AF: 0.407 AC: 857 AN: 2108

Alfa AF: 0.393 Hom.: 2088

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

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.73
DANN	Benign	0.86
PhyloP100		-1.1
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: rs820273; hg19: chr3-81547966;