rs747977871
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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.8311-16T>C 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 0.000237 in 1,582,176 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 0.00034 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00023 ( 1 hom. )
Consequence
RYR1
NM_000540.3 splice_polypyrimidine_tract, intron
NM_000540.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.529
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=-0.8).
BP6
?
Variant 19-38505293-T-C is Benign according to our data. Variant chr19-38505293-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 256572.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.8311-16T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.8311-16T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000540.3 | A2 | |||
RYR1 | ENST00000355481.8 | c.8311-16T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | P4 | ||||
RYR1 | ENST00000594335.5 | c.1763-16T>C | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 1 | |||||
RYR1 | ENST00000599547.6 | c.8311-16T>C | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000337 AC: 51AN: 151446Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000391 AC: 96AN: 245234Hom.: 0 AF XY: 0.000354 AC XY: 47AN XY: 132666
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GnomAD4 exome AF: 0.000226 AC: 324AN: 1430610Hom.: 1 Cov.: 30 AF XY: 0.000244 AC XY: 174AN XY: 712914
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GnomAD4 genome ? AF: 0.000336 AC: 51AN: 151566Hom.: 0 Cov.: 31 AF XY: 0.000257 AC XY: 19AN XY: 74050
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
RYR1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
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Name
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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