rs9870056

Positions:

• chr3-81581063-G-A
• chr3-81581063-G-T

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.1446+102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 691,076 control chromosomes in the GnomAD database, including 10,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1893 hom., cov: 31)
  • Exomes 𝑓: 0.16 (8152 hom.)
• Consequence: GBE1 NM_000158.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.289

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-81581063-G-A is Benign according to our data. Variant chr3-81581063-G-A is described in ClinVar as [Benign]. Clinvar id is 1241015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBE1	NM_000158.4	c.1446+102C>T		intron_variant		ENST00000429644.7	NP_000149.4
GBE1	XR_007095662.1	n.1574+102C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.1446+102C>T		intron_variant		1	NM_000158.4	ENSP00000410833.2
GBE1	ENST00000489715.1	c.1323+102C>T		intron_variant		2		ENSP00000419638.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23353 AN: 151242 Hom.: 1893 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.164 AC: 88781 AN: 539716 Hom.: 8152 AF XY: 0.161 AC XY: 46321 AN XY: 288536

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0975

Gnomad4 EAS exome AF: 0.0534

Gnomad4 SAS exome AF: 0.0843

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.154 AC: 23368 AN: 151360 Hom.: 1893 Cov.: 31 AF XY: 0.150 AC XY: 11075 AN XY: 73978

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.0708

Gnomad4 SAS AF: 0.0857

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.155

Alfa AF: 0.143 Hom.: 525

Bravo AF: 0.150

Asia WGS AF: 0.0920 AC: 321 AN: 3474

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	-0.92
CADD	Benign	1.2
DANN	Benign	0.62

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: rs9870056; hg19: chr3-81630214;