3-81499441-C-A

Variant names:

• chr3-81499441-C-A
• rs10511103
• NM_000158.4:c.1935-214G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000158.4(GBE1):​c.1935-214G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 152,264 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.035 (195 hom., cov: 32)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-81499441-C-A is Benign according to our data. Variant chr3-81499441-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1219802.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.116 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.1935-214G>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.1935-214G>T		intron	N/A	ENSP00000410833.2	Q04446
	GBE1	ENST00000895874.1		c.1929-214G>T		intron	N/A	ENSP00000565933.1
	GBE1	ENST00000942742.1		c.1929-214G>T		intron	N/A	ENSP00000612801.1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5248 AN: 152146 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.00813

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0345 AC: 5257 AN: 152264 Hom.: 195 Cov.: 32 AF XY: 0.0369 AC XY: 2749 AN XY: 74424

African (AFR) AF: 0.00811 AC: 337 AN: 41578

American (AMR) AF: 0.121 AC: 1848 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3468

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5190

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4828

European-Finnish (FIN) AF: 0.0520 AC: 551 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0327 AC: 2224 AN: 68012

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0230 Hom.: 22

Bravo AF: 0.0392

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.031
DANN	Benign	0.55
PhyloP100		-1.8
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: rs10511103; hg19: chr3-81548592;