3-81490255-G-T

Variant names:

• chr3-81490255-G-T
• rs9820089
• NM_000158.4:c.*152C>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.*152C>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 0.0417 in 652,126 control chromosomes in the GnomAD database, including 992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (445 hom., cov: 31)
  • Exomes 𝑓: 0.036 (547 hom.)
• Consequence: GBE1 NM_000158.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.954
• Publications: 5 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=-0.87).
• BP6: Variant 3-81490255-G-T is Benign according to our data. Variant chr3-81490255-G-T is described in ClinVar as Benign. ClinVar VariationId is 346782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 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.*152C>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.*152C>A		3_prime_UTR	Exon 16 of 16	ENSP00000410833.2	Q04446
	GBE1	ENST00000895874.1		c.*152C>A		3_prime_UTR	Exon 16 of 16	ENSP00000565933.1
	GBE1	ENST00000942742.1		c.*152C>A		3_prime_UTR	Exon 16 of 16	ENSP00000612801.1

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9123 AN: 152082 Hom.: 443 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0561

GnomAD4 exome AF: 0.0361 AC: 18037 AN: 499926 Hom.: 547 Cov.: 6 AF XY: 0.0356 AC XY: 9526 AN XY: 267732

African (AFR) AF: 0.122 AC: 1541 AN: 12630

American (AMR) AF: 0.0570 AC: 1082 AN: 18994

Ashkenazi Jewish (ASJ) AF: 0.0227 AC: 371 AN: 16340

East Asian (EAS) AF: 0.0868 AC: 2682 AN: 30910

South Asian (SAS) AF: 0.0459 AC: 2229 AN: 48598

European-Finnish (FIN) AF: 0.0315 AC: 1324 AN: 41982

Middle Eastern (MID) AF: 0.0618 AC: 148 AN: 2394

European-Non Finnish (NFE) AF: 0.0253 AC: 7604 AN: 300198

Other (OTH) AF: 0.0379 AC: 1056 AN: 27880

GnomAD4 genome AF: 0.0600 AC: 9131 AN: 152200 Hom.: 445 Cov.: 31 AF XY: 0.0606 AC XY: 4508 AN XY: 74414

African (AFR) AF: 0.124 AC: 5168 AN: 41516

American (AMR) AF: 0.0673 AC: 1029 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 80 AN: 3472

East Asian (EAS) AF: 0.0624 AC: 323 AN: 5174

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4830

European-Finnish (FIN) AF: 0.0308 AC: 327 AN: 10600

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1830 AN: 68006

Other (OTH) AF: 0.0565 AC: 119 AN: 2106

Alfa AF: 0.0336 Hom.: 171

Bravo AF: 0.0641

Asia WGS AF: 0.0600 AC: 211 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	-0.87
CADD	Benign	1.8
DANN	Benign	0.23
PhyloP100		0.95
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: rs9820089; hg19: chr3-81539406;