rs2307058

Variant names:

• chr3-81537288-G-A
• rs2307058
• NM_000158.4:c.1619-193C>T

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.1619-193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,806 control chromosomes in the GnomAD database, including 6,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6523 hom., cov: 32)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0520
• Publications: 7 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=-0.81).
• BP6: Variant 3-81537288-G-A is Benign according to our data. Variant chr3-81537288-G-A is described in ClinVar as [Benign]. Clinvar id is 1252926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBE1	NM_000158.4	c.1619-193C>T		intron_variant	Intron 12 of 15	ENST00000429644.7	NP_000149.4
GBE1	XR_007095662.1	n.1747-193C>T		intron_variant	Intron 12 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.1619-193C>T		intron_variant	Intron 12 of 15	1	NM_000158.4	ENSP00000410833.2
GBE1	ENST00000489715.1	c.1496-193C>T		intron_variant	Intron 12 of 15	2		ENSP00000419638.1
GBE1	ENST00000484687.1	n.20-193C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43791 AN: 151688 Hom.: 6516 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.289 AC: 43841 AN: 151806 Hom.: 6523 Cov.: 32 AF XY: 0.285 AC XY: 21138 AN XY: 74200

African (AFR) AF: 0.346 AC: 14346 AN: 41438

American (AMR) AF: 0.268 AC: 4072 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3466

East Asian (EAS) AF: 0.438 AC: 2246 AN: 5128

South Asian (SAS) AF: 0.163 AC: 785 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2452 AN: 10566

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18540 AN: 67856

Other (OTH) AF: 0.272 AC: 573 AN: 2110

Alfa AF: 0.275 Hom.: 26247

Bravo AF: 0.298

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 06, 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	-0.81
CADD	Benign	2.2
DANN	Benign	0.58
PhyloP100		-0.052
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: rs2307058; hg19: chr3-81586439;