rs5828009
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000540.3(RYR1):c.8932+34dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.33 ( 8550 hom., cov: 0)
Exomes 𝑓: 0.27 ( 49339 hom. )
Consequence
RYR1
NM_000540.3 intron
NM_000540.3 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.483
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 -16 ACMG points.
BP6
?
Variant 19-38507857-G-GC is Benign according to our data. Variant chr19-38507857-G-GC is described in ClinVar as [Benign]. Clinvar id is 256576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.8932+34dup | intron_variant | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.8932+34dup | intron_variant | 5 | NM_000540.3 | A2 | |||
RYR1 | ENST00000355481.8 | c.8932+34dup | intron_variant | 1 | P4 | ||||
RYR1 | ENST00000594335.5 | c.2384+34dup | intron_variant, NMD_transcript_variant | 1 | |||||
RYR1 | ENST00000599547.6 | c.8932+34dup | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.325 AC: 49168AN: 151454Hom.: 8514 Cov.: 0
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GnomAD3 exomes AF: 0.322 AC: 80321AN: 249778Hom.: 13798 AF XY: 0.322 AC XY: 43433AN XY: 135078
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GnomAD4 exome AF: 0.270 AC: 329869AN: 1223892Hom.: 49339 Cov.: 17 AF XY: 0.276 AC XY: 171019AN XY: 620590
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GnomAD4 genome ? AF: 0.325 AC: 49265AN: 151572Hom.: 8550 Cov.: 0 AF XY: 0.332 AC XY: 24565AN XY: 74008
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 28, 2013 | - - |
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 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 27, 2018 | - - |
King Denborough syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Computational scores
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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