rs34988523

Variant names:

• chr3-81499058-T-TAAG
• rs34988523
• NM_000158.4:c.2052+51_2052+52insCTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000158.4(GBE1):​c.2052+51_2052+52insCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7325 hom., cov: 0)
  • Exomes 𝑓: 0.27 (30141 hom.)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.33
• Publications: 4 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 -10 ACMG points.

• BP6: Variant 3-81499058-T-TAAG is Benign according to our data. Variant chr3-81499058-T-TAAG is described in ClinVar as Benign. ClinVar VariationId is 1252855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBE1	NM_000158.4	c.2052+51_2052+52insCTT		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+51_2052+52insCTT		intron_variant	Intron 15 of 15	1	NM_000158.4	ENSP00000410833.2
GBE1	ENST00000489715.1	c.1929+51_1929+52insCTT		intron_variant	Intron 15 of 15	2		ENSP00000419638.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46162 AN: 151608 Hom.: 7315 Cov.: 0

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.267 AC: 214163 AN: 803460 Hom.: 30141 Cov.: 11 AF XY: 0.261 AC XY: 108959 AN XY: 416880

African (AFR) AF: 0.396 AC: 7350 AN: 18542

American (AMR) AF: 0.272 AC: 7549 AN: 27740

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 3487 AN: 20100

East Asian (EAS) AF: 0.383 AC: 12623 AN: 32942

South Asian (SAS) AF: 0.156 AC: 9633 AN: 61568

European-Finnish (FIN) AF: 0.238 AC: 11489 AN: 48192

Middle Eastern (MID) AF: 0.219 AC: 954 AN: 4360

European-Non Finnish (NFE) AF: 0.273 AC: 150529 AN: 551926

Other (OTH) AF: 0.277 AC: 10549 AN: 38090

GnomAD4 genome AF: 0.305 AC: 46218 AN: 151726 Hom.: 7325 Cov.: 0 AF XY: 0.299 AC XY: 22199 AN XY: 74122

African (AFR) AF: 0.397 AC: 16415 AN: 41320

American (AMR) AF: 0.277 AC: 4225 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2184 AN: 5146

South Asian (SAS) AF: 0.163 AC: 786 AN: 4816

European-Finnish (FIN) AF: 0.230 AC: 2424 AN: 10528

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18674 AN: 67908

Other (OTH) AF: 0.294 AC: 617 AN: 2100

Alfa AF: 0.285 Hom.: 655

Bravo AF: 0.316

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 29, 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
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34988523; hg19: chr3-81548209; COSMIC: COSV107525037;