rs151309597
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000540.3(RYR1):c.7797G>A(p.Gln2599=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000129 in 1,608,114 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 0.00018 ( 0 hom., cov: 28)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
RYR1
NM_000540.3 synonymous
NM_000540.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.59
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 19-38502689-G-A is Benign according to our data. Variant chr19-38502689-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38502689-G-A is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.7797G>A | p.Gln2599= | synonymous_variant | 48/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.7797G>A | p.Gln2599= | synonymous_variant | 48/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.7797G>A | p.Gln2599= | synonymous_variant | 48/105 | 1 | P4 | ||
RYR1 | ENST00000594335.5 | c.1251G>A | p.Gln417= | synonymous_variant, NMD_transcript_variant | 9/49 | 1 | |||
RYR1 | ENST00000599547.6 | c.7797G>A | p.Gln2599= | synonymous_variant, NMD_transcript_variant | 48/80 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000179 AC: 27AN: 150996Hom.: 0 Cov.: 28
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GnomAD3 exomes AF: 0.000133 AC: 33AN: 248602Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 134684
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GnomAD4 exome AF: 0.000124 AC: 181AN: 1457118Hom.: 0 Cov.: 36 AF XY: 0.000117 AC XY: 85AN XY: 724966
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GnomAD4 genome ? AF: 0.000179 AC: 27AN: 150996Hom.: 0 Cov.: 28 AF XY: 0.000149 AC XY: 11AN XY: 73614
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | This variant is located in the RYR1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has been identified in 43/279754 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | RYR1: BP4, BP7 - |
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