rs7649028

Variant names:

• chr3-81497265-C-T
• rs7649028
• NM_000158.4:c.2052+1845G>A

Variant summary

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

The NM_000158.4(GBE1):​c.2052+1845G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,948 control chromosomes in the GnomAD database, including 7,005 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 (7005 hom., cov: 32)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Laboratory for Molecular Medicine, Ambry Genetics, G2P, ClinGen
• adult polyglucosan body disease

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GBE1	NM_000158.4	c.2052+1845G>A		intron_variant	Intron 15 of 15	ENST00000429644.7	NP_000149.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.2052+1845G>A		intron_variant	Intron 15 of 15	1	NM_000158.4	ENSP00000410833.2
GBE1	ENST00000489715.1	c.1929+1845G>A		intron_variant	Intron 15 of 15	2		ENSP00000419638.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45166 AN: 151830 Hom.: 6996 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.298 AC: 45219 AN: 151948 Hom.: 7005 Cov.: 32 AF XY: 0.293 AC XY: 21802 AN XY: 74300

African (AFR) AF: 0.376 AC: 15571 AN: 41408

American (AMR) AF: 0.270 AC: 4117 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2192 AN: 5156

South Asian (SAS) AF: 0.163 AC: 787 AN: 4814

European-Finnish (FIN) AF: 0.231 AC: 2442 AN: 10560

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

European-Non Finnish (NFE) AF: 0.274 AC: 18621 AN: 67956

Other (OTH) AF: 0.282 AC: 597 AN: 2114

Alfa AF: 0.270 Hom.: 3207

Bravo AF: 0.309

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.7
DANN	Benign	0.73
PhyloP100		0.20
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: rs7649028; hg19: chr3-81546416;