chr1-237590999-A-G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001035.3(RYR2):c.4160+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000568 in 1,602,862 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_001035.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.4160+7A>G | splice_region_variant, intron_variant | Intron 31 of 104 | 1 | NM_001035.3 | ENSP00000355533.2 | |||
RYR2 | ENST00000609119.2 | n.4160+7A>G | splice_region_variant, intron_variant | Intron 31 of 103 | 5 | ENSP00000499659.2 | ||||
RYR2 | ENST00000660292.2 | c.4160+7A>G | splice_region_variant, intron_variant | Intron 31 of 105 | ENSP00000499787.2 | |||||
RYR2 | ENST00000659194.3 | c.4160+7A>G | splice_region_variant, intron_variant | Intron 31 of 104 | ENSP00000499653.3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152138Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000748 AC: 18AN: 240572Hom.: 0 AF XY: 0.0000688 AC XY: 9AN XY: 130886
GnomAD4 exome AF: 0.0000586 AC: 85AN: 1450608Hom.: 0 Cov.: 30 AF XY: 0.0000500 AC XY: 36AN XY: 720564
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152254Hom.: 0 Cov.: 31 AF XY: 0.0000537 AC XY: 4AN XY: 74432
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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not specified Benign:1
4160+7A>G in intron 31 of RYR2: This variant is not expected to have clinical si gnificance because it is not located within the invariant +/- 1, 2 region. It ha s been identified in 1/8184 European American chromosomes from a broad populatio n by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). 41 60+7A>G in intron 31 of RYR2 (allele frequency= 1/8184) ** -
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at