rs745445082
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate
The NM_000540.3(RYR1):c.9123-6C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_000540.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.9123-6C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.9123-6C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000540.3 | A2 | |||
RYR1 | ENST00000355481.8 | c.9123-6C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | P4 | ||||
RYR1 | ENST00000594335.5 | c.2575-517C>G | intron_variant, NMD_transcript_variant | 1 | |||||
RYR1 | ENST00000599547.6 | c.9123-6C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251268Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135842
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461544Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727110
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
RYR1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at