rs11391701

Variant names:

• chr3-81761551-A-AG
• rs11391701
• NM_000158.4:c.-35dupC

Your query was ambiguous. Multiple possible variants found:

• chr3-81761551-A-AG
• chr3-81761551-A-AGG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000158.4(GBE1):​c.-35dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,588,468 control chromosomes in the GnomAD database, including 794,221 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (76173 hom., cov: 0)
  • Exomes 𝑓: 1.0 (718048 hom.)
• Consequence: GBE1 NM_000158.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.143
• Publications: 9 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 -16 ACMG points.

• BP6: Variant 3-81761551-A-AG is Benign according to our data. Variant chr3-81761551-A-AG is described in ClinVar as Benign. ClinVar VariationId is 1183062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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.-35dupC		5_prime_UTR	Exon 1 of 16	NP_000149.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBE1	ENST00000429644.7	TSL:1 MANE Select	c.-35dupC		5_prime_UTR	Exon 1 of 16	ENSP00000410833.2
	GBE1	ENST00000895874.1		c.-35dupC		5_prime_UTR	Exon 1 of 16	ENSP00000565933.1
	GBE1	ENST00000942738.1		c.-35dupC		5_prime_UTR	Exon 1 of 15	ENSP00000612797.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152231 AN: 152234 Hom.: 76114 Cov.: 0

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD2 exomes AF: 1.00 AC: 203113 AN: 203122 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 1.00 AC: 1436106 AN: 1436116 Hom.: 718048 Cov.: 36 AF XY: 1.00 AC XY: 712852 AN XY: 712858

African (AFR) AF: 1.00 AC: 32773 AN: 32776

American (AMR) AF: 1.00 AC: 40672 AN: 40672

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25678 AN: 25678

East Asian (EAS) AF: 1.00 AC: 38434 AN: 38434

South Asian (SAS) AF: 1.00 AC: 83898 AN: 83900

European-Finnish (FIN) AF: 1.00 AC: 49072 AN: 49072

Middle Eastern (MID) AF: 1.00 AC: 4394 AN: 4394

European-Non Finnish (NFE) AF: 1.00 AC: 1101789 AN: 1101792

Other (OTH) AF: 1.00 AC: 59396 AN: 59398

GnomAD4 genome AF: 1.00 AC: 152349 AN: 152352 Hom.: 76173 Cov.: 0 AF XY: 1.00 AC XY: 74504 AN XY: 74506

African (AFR) AF: 1.00 AC: 41584 AN: 41586

American (AMR) AF: 1.00 AC: 15311 AN: 15312

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5164 AN: 5164

South Asian (SAS) AF: 1.00 AC: 4830 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10630 AN: 10630

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68038 AN: 68038

Other (OTH) AF: 1.00 AC: 2114 AN: 2114

Alfa AF: 1.00 Hom.: 12629

Asia WGS AF: 1.00 AC: 3475 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Adult polyglucosan body disease (1)
-	-	1	Glycogen storage disease, type IV (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
Mutation Taster		=298/2	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: rs11391701; hg19: chr3-81810702; COSMIC: COSV70096601; COSMIC: COSV70096601;