rs757718303
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000540.3(RYR1):āc.8544C>Gā(p.Thr2848Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_000540.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.8544C>G | p.Thr2848Thr | splice_region_variant, synonymous_variant | 55/106 | ENST00000359596.8 | NP_000531.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.8544C>G | p.Thr2848Thr | splice_region_variant, synonymous_variant | 55/106 | 5 | NM_000540.3 | ENSP00000352608.2 | ||
RYR1 | ENST00000355481.8 | c.8544C>G | p.Thr2848Thr | splice_region_variant, synonymous_variant | 55/105 | 1 | ENSP00000347667.3 | |||
RYR1 | ENST00000594335.5 | n.1995C>G | splice_region_variant, non_coding_transcript_exon_variant | 16/49 | 1 | ENSP00000470927.2 | ||||
RYR1 | ENST00000599547.6 | n.8544C>G | splice_region_variant, non_coding_transcript_exon_variant | 55/80 | 2 | ENSP00000471601.2 |
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152028Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251456Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135908
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727220
GnomAD4 genome AF: 0.000191 AC: 29AN: 152028Hom.: 0 Cov.: 31 AF XY: 0.000162 AC XY: 12AN XY: 74260
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 23, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at