rs28763902
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000158.4(GBE1):c.839G>A(p.Gly280Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00334 in 1,612,910 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0037 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 20 hom. )
Consequence
GBE1
NM_000158.4 missense
NM_000158.4 missense
Scores
6
8
4
Clinical Significance
Conservation
PhyloP100: 4.66
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013617814).
BP6
?
Variant 3-81642934-C-T is Benign according to our data. Variant chr3-81642934-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-81642934-C-T is described in Lovd as [Likely_benign].
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GBE1 | NM_000158.4 | c.839G>A | p.Gly280Asp | missense_variant | 7/16 | ENST00000429644.7 | |
GBE1 | XR_007095662.1 | n.967G>A | non_coding_transcript_exon_variant | 7/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GBE1 | ENST00000429644.7 | c.839G>A | p.Gly280Asp | missense_variant | 7/16 | 1 | NM_000158.4 | P1 | |
GBE1 | ENST00000489715.1 | c.716G>A | p.Gly239Asp | missense_variant | 7/16 | 2 | |||
GBE1 | ENST00000498468.1 | n.389G>A | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00370 AC: 562AN: 151982Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00408 AC: 1013AN: 248014Hom.: 5 AF XY: 0.00398 AC XY: 536AN XY: 134560
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GnomAD4 exome AF: 0.00330 AC: 4822AN: 1460810Hom.: 20 Cov.: 30 AF XY: 0.00326 AC XY: 2369AN XY: 726686
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GnomAD4 genome ? AF: 0.00369 AC: 562AN: 152100Hom.: 6 Cov.: 32 AF XY: 0.00476 AC XY: 354AN XY: 74352
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 13, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 27, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 17, 2015 | - - |
Glycogen storage disease, type IV Benign:2
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 10, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 23, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | GBE1: PP3, BS2 - |
Glycogen storage disease, type IV;C1849722:Adult polyglucosan body disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 07, 2022 | - - |
Adult polyglucosan body disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Glycogen storage disease, type IV;C1856301:Glycogen storage disease IV, classic hepatic Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at