rs118126378
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_000540.3(RYR1):c.14505G>A(p.Gly4835Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,614,194 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000540.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00329 AC: 501AN: 152216Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.00311 AC: 782AN: 251144Hom.: 2 AF XY: 0.00315 AC XY: 427AN XY: 135770
GnomAD4 exome AF: 0.00381 AC: 5564AN: 1461860Hom.: 18 Cov.: 33 AF XY: 0.00377 AC XY: 2742AN XY: 727232
GnomAD4 genome AF: 0.00329 AC: 501AN: 152334Hom.: 1 Cov.: 31 AF XY: 0.00324 AC XY: 241AN XY: 74480
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:5
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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. -
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not provided Benign:5
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RYR1: BP4, BP7, BS2 -
Malignant hyperthermia, susceptibility to, 1 Benign:3
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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. -
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Congenital multicore myopathy with external ophthalmoplegia Benign:1
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. -
RYR1-related disorder Benign:1
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Neuromuscular disease, congenital, with uniform type 1 fiber Benign:1
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Central core myopathy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at