rs576773729
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000540.3(RYR1):c.8068-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,714 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 1 hom. )
Consequence
RYR1
NM_000540.3 splice_polypyrimidine_tract, intron
NM_000540.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001586
2
Clinical Significance
Conservation
PhyloP100: -0.0940
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=-0.9).
BP6
?
Variant 19-38504736-C-T is Benign according to our data. Variant chr19-38504736-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 590605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.8068-12C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.8068-12C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000540.3 | A2 | |||
RYR1 | ENST00000355481.8 | c.8068-12C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | P4 | ||||
RYR1 | ENST00000594335.5 | c.1520-12C>T | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 1 | |||||
RYR1 | ENST00000599547.6 | c.8068-12C>T | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152098Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251388Hom.: 1 AF XY: 0.0000515 AC XY: 7AN XY: 135896
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461616Hom.: 1 Cov.: 43 AF XY: 0.0000165 AC XY: 12AN XY: 727118
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74282
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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 | Nov 20, 2023 | - - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 05, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at