rs3745850
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_000540.3(RYR1):c.3557-74C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,605,482 control chromosomes in the GnomAD database, including 69 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 0.0023 ( 10 hom., cov: 31)
Exomes 𝑓: 0.0024 ( 59 hom. )
Consequence
RYR1
NM_000540.3 intron
NM_000540.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.57
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00235 (357/152154) while in subpopulation EAS AF= 0.0389 (201/5162). AF 95% confidence interval is 0.0345. There are 10 homozygotes in gnomad4. There are 220 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High Homozygotes in GnomAd4 at 10 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.3557-74C>T | intron_variant | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.3557-74C>T | intron_variant | 5 | NM_000540.3 | A2 | |||
RYR1 | ENST00000355481.8 | c.3557-74C>T | intron_variant | 1 | P4 | ||||
RYR1 | ENST00000599547.6 | c.3557-74C>T | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00233 AC: 354AN: 152036Hom.: 9 Cov.: 31
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GnomAD4 exome AF: 0.00244 AC: 3546AN: 1453328Hom.: 59 Cov.: 30 AF XY: 0.00308 AC XY: 2226AN XY: 723452
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GnomAD4 genome ? AF: 0.00235 AC: 357AN: 152154Hom.: 10 Cov.: 31 AF XY: 0.00296 AC XY: 220AN XY: 74406
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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
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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