rs9863136

Positions:

• chr3-81671070-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000158.4(GBE1):​c.314-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 482,392 control chromosomes in the GnomAD database, including 5,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1431 hom., cov: 32)
  • Exomes 𝑓: 0.14 (3727 hom.)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0300

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-81671070-T-C is Benign according to our data. Variant chr3-81671070-T-C is described in ClinVar as [Benign]. Clinvar id is 1270555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBE1	NM_000158.4	c.314-117A>G		intron_variant		ENST00000429644.7	NP_000149.4
GBE1	XR_007095662.1	n.442-117A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.314-117A>G		intron_variant		1	NM_000158.4	ENSP00000410833	P1
GBE1	ENST00000489715.1	c.191-117A>G		intron_variant		2		ENSP00000419638

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20013 AN: 152112 Hom.: 1432 Cov.: 32

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.0763

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.147

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.143 AC: 47115 AN: 330162 Hom.: 3727 AF XY: 0.141 AC XY: 24097 AN XY: 170924

Gnomad4 AFR exome AF: 0.0817

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0855

Gnomad4 EAS exome AF: 0.0685

Gnomad4 SAS exome AF: 0.0597

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.132 AC: 20022 AN: 152230 Hom.: 1431 Cov.: 32 AF XY: 0.127 AC XY: 9441 AN XY: 74420

Gnomad4 AFR AF: 0.0901

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.0769

Gnomad4 SAS AF: 0.0696

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.139

Alfa AF: 0.143 Hom.: 200

Bravo AF: 0.130

Asia WGS AF: 0.0800 AC: 279 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.83
DANN	Benign	0.45

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: rs9863136; hg19: chr3-81720221;