rs193074572
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000158.4(GBE1):c.2017G>A(p.Ala673Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00781 in 1,609,962 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000158.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GBE1 | NM_000158.4 | c.2017G>A | p.Ala673Thr | missense_variant | 15/16 | ENST00000429644.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GBE1 | ENST00000429644.7 | c.2017G>A | p.Ala673Thr | missense_variant | 15/16 | 1 | NM_000158.4 | P1 | |
GBE1 | ENST00000489715.1 | c.1894G>A | p.Ala632Thr | missense_variant | 15/16 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00514 AC: 782AN: 152070Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00502 AC: 1235AN: 246198Hom.: 5 AF XY: 0.00521 AC XY: 695AN XY: 133462
GnomAD4 exome AF: 0.00809 AC: 11799AN: 1457774Hom.: 58 Cov.: 29 AF XY: 0.00798 AC XY: 5790AN XY: 725116
GnomAD4 genome ? AF: 0.00514 AC: 782AN: 152188Hom.: 6 Cov.: 32 AF XY: 0.00482 AC XY: 359AN XY: 74412
ClinVar
Submissions by phenotype
not provided Benign:6
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | GBE1: BP4, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 10, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2020 | This variant is associated with the following publications: (PMID: 26670585, 31862442) - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 08, 2022 | Variant summary: GBE1 c.2017G>A (p.Ala673Thr) results in a non-conservative amino acid change located in the Alpha-amylase/branching enzyme, C-terminal all beta domain (IPR006048) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.005 in 277576 control chromosomes (gnomAD), predominantly at a frequency of 0.0083 within the Non-Finnish European subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 6 fold of the estimated maximal expected allele frequency for a pathogenic variant in GBE1 causing Glycogen Storage Disease, Type IV (0.0013), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. Six ClinVar submitters have assessed the variant since 2014: one classified the variant as likely benign, and five as benign. Based on the evidence outlined above, the variant was classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 17, 2016 | - - |
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 12, 2022 | - - |
Glycogen storage disease, type IV Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Adult polyglucosan body disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at