rs7622741

Variant names:

• chr3-81501164-A-G
• rs7622741
• NM_000158.4:c.1935-1937T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000158.4(GBE1):​c.1935-1937T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,110 control chromosomes in the GnomAD database, including 7,158 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7158 hom., cov: 32)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 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.1935-1937T>C		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.1935-1937T>C		intron	N/A	ENSP00000410833.2	Q04446
	GBE1	ENST00000895874.1		c.1929-1937T>C		intron	N/A	ENSP00000565933.1
	GBE1	ENST00000942742.1		c.1929-1937T>C		intron	N/A	ENSP00000612801.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45736 AN: 151992 Hom.: 7152 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.301 AC: 45784 AN: 152110 Hom.: 7158 Cov.: 32 AF XY: 0.296 AC XY: 22029 AN XY: 74376

African (AFR) AF: 0.383 AC: 15880 AN: 41458

American (AMR) AF: 0.277 AC: 4238 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3468

East Asian (EAS) AF: 0.428 AC: 2214 AN: 5174

South Asian (SAS) AF: 0.164 AC: 793 AN: 4830

European-Finnish (FIN) AF: 0.232 AC: 2454 AN: 10592

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18705 AN: 67986

Other (OTH) AF: 0.289 AC: 610 AN: 2112

Alfa AF: 0.280 Hom.: 20760

Bravo AF: 0.313

Asia WGS AF: 0.292 AC: 1016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.63
PhyloP100		0.35
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: rs7622741; hg19: chr3-81550315;