rs114203198
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_000540.3(RYR1):c.5634G>C(p.Glu1878Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,611,380 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000540.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.5634G>C | p.Glu1878Asp | missense_variant | 35/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.5634G>C | p.Glu1878Asp | missense_variant | 35/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.5634G>C | p.Glu1878Asp | missense_variant | 35/105 | 1 | P4 | ||
RYR1 | ENST00000599547.6 | c.5634G>C | p.Glu1878Asp | missense_variant, NMD_transcript_variant | 35/80 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00439 AC: 668AN: 152126Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00113 AC: 280AN: 248306Hom.: 1 AF XY: 0.000818 AC XY: 110AN XY: 134476
GnomAD4 exome AF: 0.000550 AC: 802AN: 1459136Hom.: 7 Cov.: 32 AF XY: 0.000479 AC XY: 348AN XY: 726028
GnomAD4 genome ? AF: 0.00446 AC: 679AN: 152244Hom.: 4 Cov.: 32 AF XY: 0.00443 AC XY: 330AN XY: 74442
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 31, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 02, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
Central core myopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
RYR1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Malignant hyperthermia, susceptibility to, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Malignant hyperthermia of anesthesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 04, 2020 | This variant is associated with the following publications: (PMID: 30325262) - |
Multiminicore myopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Neuromuscular disease, congenital, with uniform type 1 fiber Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at