rs750987143
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000540.3(RYR1):c.10440+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000540.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.10440+7G>A | splice_region_variant, intron_variant | ENST00000359596.8 | NP_000531.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.10440+7G>A | splice_region_variant, intron_variant | 5 | NM_000540.3 | ENSP00000352608 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152200Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251232Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135818
GnomAD4 exome AF: 0.000120 AC: 175AN: 1461842Hom.: 0 Cov.: 33 AF XY: 0.000110 AC XY: 80AN XY: 727216
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152200Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 29, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | RYR1: PM2, BP4 - |
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at