chr3-81490231-C-T

Variant names:

• chr3-81490231-C-T
• rs846
• NM_000158.4:c.*176G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000158.4(GBE1):​c.*176G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 587,666 control chromosomes in the GnomAD database, including 54,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11426 hom., cov: 32)
  • Exomes 𝑓: 0.43 (43270 hom.)
• Consequence: GBE1 NM_000158.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0750
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-81490231-C-T is Benign according to our data. Variant chr3-81490231-C-T is described in ClinVar as Benign. ClinVar VariationId is 346781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 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.*176G>A		3_prime_UTR	Exon 16 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.*176G>A		3_prime_UTR	Exon 16 of 16	ENSP00000410833.2	Q04446
	GBE1	ENST00000895874.1		c.*176G>A		3_prime_UTR	Exon 16 of 16	ENSP00000565933.1
	GBE1	ENST00000942742.1		c.*176G>A		3_prime_UTR	Exon 16 of 16	ENSP00000612801.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55393 AN: 151922 Hom.: 11420 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.0852

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

GnomAD4 exome AF: 0.432 AC: 187997 AN: 435624 Hom.: 43270 Cov.: 4 AF XY: 0.441 AC XY: 102264 AN XY: 231764

African (AFR) AF: 0.189 AC: 2068 AN: 10924

American (AMR) AF: 0.417 AC: 6063 AN: 14556

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 8278 AN: 13950

East Asian (EAS) AF: 0.140 AC: 4000 AN: 28490

South Asian (SAS) AF: 0.570 AC: 22556 AN: 39586

European-Finnish (FIN) AF: 0.380 AC: 13081 AN: 34464

Middle Eastern (MID) AF: 0.567 AC: 1129 AN: 1990

European-Non Finnish (NFE) AF: 0.451 AC: 120105 AN: 266458

Other (OTH) AF: 0.425 AC: 10717 AN: 25206

GnomAD4 genome AF: 0.364 AC: 55411 AN: 152042 Hom.: 11426 Cov.: 32 AF XY: 0.365 AC XY: 27108 AN XY: 74302

African (AFR) AF: 0.185 AC: 7679 AN: 41480

American (AMR) AF: 0.419 AC: 6394 AN: 15270

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

East Asian (EAS) AF: 0.0852 AC: 440 AN: 5164

South Asian (SAS) AF: 0.549 AC: 2649 AN: 4824

European-Finnish (FIN) AF: 0.395 AC: 4173 AN: 10564

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30430 AN: 67954

Other (OTH) AF: 0.406 AC: 860 AN: 2116

Alfa AF: 0.376 Hom.: 2131

Bravo AF: 0.352

Asia WGS AF: 0.304 AC: 1057 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Adult polyglucosan body disease (1)
-	-	1	Glycogen storage disease, type IV (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.97
DANN	Benign	0.52
PhyloP100		0.075
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: rs846; hg19: chr3-81539382; COSMIC: COSV70103732;