rs775494152
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000540.3(RYR1):c.13999-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,312 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00046 ( 1 hom., cov: 31)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
RYR1
NM_000540.3 intron
NM_000540.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.198
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 19-38573158-G-A is Benign according to our data. Variant chr19-38573158-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 590444.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.13999-19G>A | intron_variant | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.13999-19G>A | intron_variant | 5 | NM_000540.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000460 AC: 70AN: 152194Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251242Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135802
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GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461118Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 726864
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GnomAD4 genome ? AF: 0.000460 AC: 70AN: 152194Hom.: 1 Cov.: 31 AF XY: 0.000430 AC XY: 32AN XY: 74346
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 30, 2013 | - - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at