rs9820490

Variant names:

• chr3-81761365-C-A
• rs9820490
• NM_000158.4:c.143+10G>T

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.143+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,601,546 control chromosomes in the GnomAD database, including 19,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1324 hom., cov: 33)
  • Exomes 𝑓: 0.16 (18594 hom.)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -4.83
• 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=-0.68).
• BP6: Variant 3-81761365-C-A is Benign according to our data. Variant chr3-81761365-C-A is described in ClinVar as Benign. ClinVar VariationId is 255382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 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.143+10G>T		intron	N/A	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.143+10G>T		intron	N/A	ENSP00000410833.2	Q04446
	GBE1	ENST00000895874.1		c.143+10G>T		intron	N/A	ENSP00000565933.1
	GBE1	ENST00000942742.1		c.143+10G>T		intron	N/A	ENSP00000612801.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18760 AN: 152150 Hom.: 1325 Cov.: 33

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0759

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.122 AC: 29371 AN: 241116 AF XY: 0.122

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.0721

Gnomad ASJ exome AF: 0.0798

Gnomad EAS exome AF: 0.0722

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.155 AC: 224887 AN: 1449278 Hom.: 18594 Cov.: 33 AF XY: 0.153 AC XY: 109970 AN XY: 719284

African (AFR) AF: 0.0596 AC: 1931 AN: 32380

American (AMR) AF: 0.0774 AC: 3428 AN: 44290

Ashkenazi Jewish (ASJ) AF: 0.0828 AC: 2137 AN: 25798

East Asian (EAS) AF: 0.0703 AC: 2720 AN: 38692

South Asian (SAS) AF: 0.0668 AC: 5739 AN: 85970

European-Finnish (FIN) AF: 0.138 AC: 7325 AN: 53230

Middle Eastern (MID) AF: 0.123 AC: 696 AN: 5644

European-Non Finnish (NFE) AF: 0.174 AC: 192418 AN: 1103604

Other (OTH) AF: 0.142 AC: 8493 AN: 59670

GnomAD4 genome AF: 0.123 AC: 18762 AN: 152268 Hom.: 1324 Cov.: 33 AF XY: 0.119 AC XY: 8873 AN XY: 74454

African (AFR) AF: 0.0635 AC: 2639 AN: 41560

American (AMR) AF: 0.104 AC: 1590 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.0764 AC: 395 AN: 5168

South Asian (SAS) AF: 0.0656 AC: 317 AN: 4830

European-Finnish (FIN) AF: 0.138 AC: 1462 AN: 10604

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11617 AN: 68010

Other (OTH) AF: 0.135 AC: 285 AN: 2112

Alfa AF: 0.135 Hom.: 913

Bravo AF: 0.120

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	Glycogen storage disease, type IV (3)
-	-	2	Adult polyglucosan body disease (2)
-	-	2	not provided (2)
-	-	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	-0.68
CADD	Benign	0.13
DANN	Benign	0.85
PhyloP100		-4.8
PromoterAI		-0.0028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs9820490; hg19: chr3-81810516; COSMIC: COSV70101000; COSMIC: COSV70101000;