rs7254832
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000540.3(RYR1):c.1441-24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 1,613,088 control chromosomes in the GnomAD database, including 619,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.90 ( 61475 hom., cov: 30)
Exomes 𝑓: 0.87 ( 558516 hom. )
Consequence
RYR1
NM_000540.3 intron
NM_000540.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0410
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 19-38455211-T-C is Benign according to our data. Variant chr19-38455211-T-C is described in ClinVar as [Benign]. Clinvar id is 133065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38455211-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.1441-24T>C | intron_variant | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.1441-24T>C | intron_variant | 5 | NM_000540.3 | A2 | |||
RYR1 | ENST00000355481.8 | c.1441-24T>C | intron_variant | 1 | P4 | ||||
RYR1 | ENST00000599547.6 | c.1441-24T>C | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.898 AC: 136508AN: 152024Hom.: 61439 Cov.: 30
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GnomAD3 exomes AF: 0.882 AC: 221876AN: 251434Hom.: 98387 AF XY: 0.874 AC XY: 118800AN XY: 135894
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GnomAD4 exome AF: 0.873 AC: 1275841AN: 1460946Hom.: 558516 Cov.: 41 AF XY: 0.869 AC XY: 631724AN XY: 726856
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GnomAD4 genome ? AF: 0.898 AC: 136602AN: 152142Hom.: 61475 Cov.: 30 AF XY: 0.898 AC XY: 66818AN XY: 74368
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ClinVar
Significance: Benign
Submissions summary: Benign:5Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
not provided, no classification provided | literature only | Leiden Muscular Dystrophy (RYR1) | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 04, 2016 | - - |
Congenital multicore myopathy with external ophthalmoplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Central core myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
King Denborough syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 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