rs377100871
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000540.3(RYR1):āc.4902C>Gā(p.Thr1634=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,558,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00060 ( 0 hom., cov: 31)
Exomes š: 0.00010 ( 0 hom. )
Consequence
RYR1
NM_000540.3 synonymous
NM_000540.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.387
Genes affected
RYR1 (HGNC:10483): (ryanodine receptor 1) This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 19-38483484-C-G is Benign according to our data. Variant chr19-38483484-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 256521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.387 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.4902C>G | p.Thr1634= | synonymous_variant | 33/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.4902C>G | p.Thr1634= | synonymous_variant | 33/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.4902C>G | p.Thr1634= | synonymous_variant | 33/105 | 1 | P4 | ||
RYR1 | ENST00000599547.6 | c.4902C>G | p.Thr1634= | synonymous_variant, NMD_transcript_variant | 33/80 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000598 AC: 91AN: 152100Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000163 AC: 27AN: 165594Hom.: 0 AF XY: 0.000101 AC XY: 9AN XY: 89068
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GnomAD4 exome AF: 0.000100 AC: 141AN: 1406134Hom.: 0 Cov.: 32 AF XY: 0.0000834 AC XY: 58AN XY: 695238
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GnomAD4 genome ? AF: 0.000604 AC: 92AN: 152218Hom.: 0 Cov.: 31 AF XY: 0.000591 AC XY: 44AN XY: 74428
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 22, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Malignant hyperthermia, susceptibility to, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 18, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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