rs369456396
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_000540.3(RYR1):c.7092C>T(p.Phe2364=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,600,884 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 (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
RYR1
NM_000540.3 synonymous
NM_000540.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.17
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
?
Variant 19-38499699-C-T is Benign according to our data. Variant chr19-38499699-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 478268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.17 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.7092C>T | p.Phe2364= | synonymous_variant | 44/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.7092C>T | p.Phe2364= | synonymous_variant | 44/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.7092C>T | p.Phe2364= | synonymous_variant | 44/105 | 1 | P4 | ||
RYR1 | ENST00000594335.5 | c.546C>T | p.Phe182= | synonymous_variant, NMD_transcript_variant | 5/49 | 1 | |||
RYR1 | ENST00000599547.6 | c.7092C>T | p.Phe2364= | synonymous_variant, NMD_transcript_variant | 44/80 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000168 AC: 4AN: 238770Hom.: 0 AF XY: 0.0000230 AC XY: 3AN XY: 130532
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GnomAD4 exome AF: 0.0000159 AC: 23AN: 1448616Hom.: 0 Cov.: 35 AF XY: 0.0000194 AC XY: 14AN XY: 721068
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74456
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Malignant hyperthermia, susceptibility to, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 23, 2018 | - - |
Congenital myopathy with fiber type disproportion;C0751951:Central core myopathy;C1840365:King Denborough syndrome;C1850674:Congenital multicore myopathy with external ophthalmoplegia;C2930980:Malignant hyperthermia, susceptibility to, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 06, 2021 | - - |
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