rs62267114
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000158.4(GBE1):c.15G>A(p.Met5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,604,598 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000158.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00117 AC: 178AN: 152142Hom.: 1 Cov.: 34
GnomAD3 exomes AF: 0.000861 AC: 195AN: 226356Hom.: 0 AF XY: 0.000848 AC XY: 106AN XY: 124930
GnomAD4 exome AF: 0.00154 AC: 2243AN: 1452456Hom.: 2 Cov.: 33 AF XY: 0.00147 AC XY: 1062AN XY: 722230
GnomAD4 genome AF: 0.00117 AC: 178AN: 152142Hom.: 1 Cov.: 34 AF XY: 0.00112 AC XY: 83AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:3
BP4 -
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Identified in a family with familial primary hyperparathyroidism in published literature (PMID: 27745835); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27745835) -
Glycogen storage disease, type IV Uncertain:1Other:1
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Glycogen storage disease, type IV;C1849722:Adult polyglucosan body disease Uncertain:1
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Adult polyglucosan body disease Uncertain:1
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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not specified Benign:1
Variant summary: GBE1 c.15G>A (p.Met5Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00093 in 257704 control chromosomes, predominantly at a frequency of 0.0017 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygote. To our knowledge, no occurrence of c.15G>A in individuals affected with GBE1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. -
GBE1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Glycogen storage disease, type IV;C1856301:Glycogen storage disease IV, classic hepatic Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at