rs151091415

Positions:

• chr3-81670803-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000158.4(GBE1):​c.429+35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,137,706 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (21 hom.)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.227

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-81670803-A-G is Benign according to our data. Variant chr3-81670803-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 255389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBE1	NM_000158.4	c.429+35T>C		intron_variant		ENST00000429644.7	NP_000149.4
GBE1	XR_007095662.1	n.557+35T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.429+35T>C		intron_variant		1	NM_000158.4	ENSP00000410833.2
GBE1	ENST00000489715.1	c.306+35T>C		intron_variant		2		ENSP00000419638.1
GBE1	ENST00000477426.1	n.145+35T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00380 AC: 579 AN: 152196 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00604

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00432 AC: 480 AN: 111002 Hom.: 2 AF XY: 0.00380 AC XY: 228 AN XY: 60016

Gnomad AFR exome AF: 0.00176

Gnomad AMR exome AF: 0.00132

Gnomad ASJ exome AF: 0.00614

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00191

Gnomad FIN exome AF: 0.00512

Gnomad NFE exome AF: 0.00565

Gnomad OTH exome AF: 0.00645

GnomAD4 exome AF: 0.00476 AC: 4688 AN: 985392 Hom.: 21 Cov.: 12 AF XY: 0.00470 AC XY: 2355 AN XY: 500586

Gnomad4 AFR exome AF: 0.00139

Gnomad4 AMR exome AF: 0.00147

Gnomad4 ASJ exome AF: 0.00640

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00203

Gnomad4 FIN exome AF: 0.00550

Gnomad4 NFE exome AF: 0.00522

Gnomad4 OTH exome AF: 0.00487

GnomAD4 genome AF: 0.00378 AC: 576 AN: 152314 Hom.: 3 Cov.: 32 AF XY: 0.00365 AC XY: 272 AN XY: 74474

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.00603

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00557 Hom.: 2

Bravo AF: 0.00340

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs151091415; hg19: chr3-81719954;