rs9863136

Variant names:

• chr3-81671070-T-C
• rs9863136
• NM_000158.4:c.314-117A>G

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.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
• Publications: 2 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: Ambry Genetics, Laboratory for Molecular Medicine, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• adult polyglucosan body disease

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000158.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBE1	NM_000158.4	MANE Select	c.314-117A>G		intron	N/A	NP_000149.4	Q04446

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBE1	ENST00000429644.7	TSL:1 MANE Select	c.314-117A>G		intron	N/A	ENSP00000410833.2	Q04446
	GBE1	ENST00000895874.1		c.314-117A>G		intron	N/A	ENSP00000565933.1
	GBE1	ENST00000942742.1		c.314-117A>G		intron	N/A	ENSP00000612801.1

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

African (AFR) AF: 0.0817 AC: 625 AN: 7648

American (AMR) AF: 0.103 AC: 815 AN: 7904

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 933 AN: 10912

East Asian (EAS) AF: 0.0685 AC: 1579 AN: 23062

South Asian (SAS) AF: 0.0597 AC: 1006 AN: 16852

European-Finnish (FIN) AF: 0.135 AC: 4260 AN: 31588

Middle Eastern (MID) AF: 0.131 AC: 250 AN: 1902

European-Non Finnish (NFE) AF: 0.166 AC: 34818 AN: 210250

Other (OTH) AF: 0.141 AC: 2829 AN: 20044

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

African (AFR) AF: 0.0901 AC: 3744 AN: 41554

American (AMR) AF: 0.109 AC: 1668 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.0769 AC: 399 AN: 5188

South Asian (SAS) AF: 0.0696 AC: 336 AN: 4828

European-Finnish (FIN) AF: 0.138 AC: 1459 AN: 10598

Middle Eastern (MID) AF: 0.145 AC: 42 AN: 290

European-Non Finnish (NFE) AF: 0.172 AC: 11662 AN: 67990

Other (OTH) AF: 0.139 AC: 294 AN: 2112

Alfa AF: 0.141 Hom.: 208

Bravo AF: 0.130

Asia WGS AF: 0.0800 AC: 279 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.83
DANN	Benign	0.45
PhyloP100		-0.030
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: rs9863136; hg19: chr3-81720221;