chr3-81581063-G-A

Variant names:

• chr3-81581063-G-A
• rs9870056
• NM_000158.4:c.1446+102C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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 VariationId 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 rank	MANE	Protein	UniProt
GBE1	NM_000158.4	c.1446+102C>T		intron_variant	Intron 11 of 15	ENST00000429644.7	NP_000149.4
GBE1	XR_007095662.1	n.1574+102C>T		intron_variant	Intron 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBE1	ENST00000429644.7	c.1446+102C>T		intron_variant	Intron 11 of 15	1	NM_000158.4	ENSP00000410833.2
GBE1	ENST00000489715.1	c.1323+102C>T		intron_variant	Intron 11 of 15	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

African (AFR) AF: 0.106 AC: 1406 AN: 13250

American (AMR) AF: 0.103 AC: 2162 AN: 21070

Ashkenazi Jewish (ASJ) AF: 0.0975 AC: 1670 AN: 17126

East Asian (EAS) AF: 0.0534 AC: 1647 AN: 30870

South Asian (SAS) AF: 0.0843 AC: 4141 AN: 49110

European-Finnish (FIN) AF: 0.158 AC: 6196 AN: 39132

Middle Eastern (MID) AF: 0.137 AC: 512 AN: 3746

European-Non Finnish (NFE) AF: 0.197 AC: 66317 AN: 336124

Other (OTH) AF: 0.162 AC: 4730 AN: 29288

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

African (AFR) AF: 0.110 AC: 4533 AN: 41238

American (AMR) AF: 0.131 AC: 1981 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 322 AN: 3446

East Asian (EAS) AF: 0.0708 AC: 364 AN: 5140

South Asian (SAS) AF: 0.0857 AC: 410 AN: 4784

European-Finnish (FIN) AF: 0.158 AC: 1661 AN: 10520

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.200 AC: 13559 AN: 67792

Other (OTH) AF: 0.155 AC: 325 AN: 2094

Alfa AF: 0.151 Hom.: 658

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		0.29
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: rs9870056; hg19: chr3-81630214;