rs2307058

Positions:

• chr3-81537288-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000158.4(GBE1):​c.1619-193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,806 control chromosomes in the GnomAD database, including 6,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6523 hom., cov: 32)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0520

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-81537288-G-A is Benign according to our data. Variant chr3-81537288-G-A is described in ClinVar as [Benign]. Clinvar id is 1252926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GBE1	NM_000158.4	c.1619-193C>T		intron_variant		ENST00000429644.7
GBE1	XR_007095662.1	n.1747-193C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBE1	ENST00000429644.7	c.1619-193C>T		intron_variant		1	NM_000158.4	P1
GBE1	ENST00000489715.1	c.1496-193C>T		intron_variant		2
GBE1	ENST00000484687.1	n.20-193C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43791 AN: 151688 Hom.: 6516 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.289 AC: 43841 AN: 151806 Hom.: 6523 Cov.: 32 AF XY: 0.285 AC XY: 21138 AN XY: 74200

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.272

Alfa AF: 0.268 Hom.: 12404

Bravo AF: 0.298

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.58

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: rs2307058; hg19: chr3-81586439;