rs2071090
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000540.3(RYR1):c.10456-518T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,130 control chromosomes in the GnomAD database, including 1,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: 𝑓 0.15 ( 1871 hom., cov: 31)
Consequence
RYR1
NM_000540.3 intron
NM_000540.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.650
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=-0.88).
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.10456-518T>C | intron_variant | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.10456-518T>C | intron_variant | 5 | NM_000540.3 | A2 | |||
RYR1 | ENST00000355481.8 | c.10441-518T>C | intron_variant | 1 | P4 | ||||
RYR1 | ENST00000594335.5 | c.*1184-518T>C | intron_variant, NMD_transcript_variant | 1 | |||||
RYR1 | ENST00000599547.6 | c.*1215-518T>C | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.149 AC: 22588AN: 152012Hom.: 1861 Cov.: 31
GnomAD3 genomes
?
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31
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.149 AC: 22636AN: 152130Hom.: 1871 Cov.: 31 AF XY: 0.152 AC XY: 11276AN XY: 74392
GnomAD4 genome
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31
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11276
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74392
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1108
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3478
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not provided Other:1
not provided, no classification provided | literature only | Leiden Muscular Dystrophy (RYR1) | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
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