rs13320194

Variant names:

• chr3-81670925-G-A
• rs13320194
• NM_000158.4:c.342C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-81670925-G-A
• chr3-81670925-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000158.4(GBE1):​c.342C>T​(p.Tyr114Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,565,734 control chromosomes in the GnomAD database, including 2,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (1141 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1642 hom.)
• Consequence: GBE1 NM_000158.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.736
• Publications: 6 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: Ambry Genetics, Laboratory for Molecular Medicine, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• adult polyglucosan body disease

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 3-81670925-G-A is Benign according to our data. Variant chr3-81670925-G-A is described in ClinVar as Benign. ClinVar VariationId is 255388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.736 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000158.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBE1	NM_000158.4	MANE Select	c.342C>T	p.Tyr114Tyr	synonymous	Exon 3 of 16	NP_000149.4	Q04446

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBE1	ENST00000429644.7	TSL:1 MANE Select	c.342C>T	p.Tyr114Tyr	synonymous	Exon 3 of 16	ENSP00000410833.2	Q04446
	GBE1	ENST00000895874.1		c.342C>T	p.Tyr114Tyr	synonymous	Exon 3 of 16	ENSP00000565933.1
	GBE1	ENST00000942742.1		c.342C>T	p.Tyr114Tyr	synonymous	Exon 3 of 16	ENSP00000612801.1

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12914 AN: 151998 Hom.: 1141 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.00585

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0751

GnomAD2 exomes AF: 0.0397 AC: 7883 AN: 198448 AF XY: 0.0364

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.0577

Gnomad ASJ exome AF: 0.0256

Gnomad EAS exome AF: 0.0562

Gnomad FIN exome AF: 0.00365

Gnomad NFE exome AF: 0.0206

Gnomad OTH exome AF: 0.0314

GnomAD4 exome AF: 0.0322 AC: 45474 AN: 1413618 Hom.: 1642 Cov.: 28 AF XY: 0.0318 AC XY: 22305 AN XY: 700776

African (AFR) AF: 0.220 AC: 6767 AN: 30780

American (AMR) AF: 0.0605 AC: 2250 AN: 37166

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 706 AN: 25318

East Asian (EAS) AF: 0.0867 AC: 3235 AN: 37292

South Asian (SAS) AF: 0.0403 AC: 3122 AN: 77412

European-Finnish (FIN) AF: 0.00562 AC: 294 AN: 52294

Middle Eastern (MID) AF: 0.0619 AC: 353 AN: 5700

European-Non Finnish (NFE) AF: 0.0241 AC: 26280 AN: 1089168

Other (OTH) AF: 0.0422 AC: 2467 AN: 58488

GnomAD4 genome AF: 0.0850 AC: 12923 AN: 152116 Hom.: 1141 Cov.: 32 AF XY: 0.0831 AC XY: 6177 AN XY: 74358

African (AFR) AF: 0.223 AC: 9242 AN: 41454

American (AMR) AF: 0.0751 AC: 1148 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3470

East Asian (EAS) AF: 0.0739 AC: 383 AN: 5180

South Asian (SAS) AF: 0.0352 AC: 170 AN: 4824

European-Finnish (FIN) AF: 0.00585 AC: 62 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0239 AC: 1626 AN: 67990

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.0478 Hom.: 1382

Bravo AF: 0.0960

Asia WGS AF: 0.0610 AC: 211 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Glycogen storage disease, type IV (2)
-	-	2	not provided (2)
-	-	1	Adult polyglucosan body disease (1)
-	-	1	Glycogen storage disease, type IV;C1856301:Glycogen storage disease IV, classic hepatic (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		0.74
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: rs13320194; hg19: chr3-81720076; COSMIC: COSV70097732;