rs148907377
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000540.3(RYR1):c.7878G>A(p.Leu2626=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,611,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L2626L) has been classified as Likely benign.
Frequency
Consequence
NM_000540.3 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 | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.7878G>A | p.Leu2626= | synonymous_variant | 49/106 | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.7878G>A | p.Leu2626= | synonymous_variant | 49/106 | 5 | NM_000540.3 | A2 | |
RYR1 | ENST00000355481.8 | c.7878G>A | p.Leu2626= | synonymous_variant | 49/105 | 1 | P4 | ||
RYR1 | ENST00000594335.5 | c.1332G>A | p.Leu444= | synonymous_variant, NMD_transcript_variant | 10/49 | 1 | |||
RYR1 | ENST00000599547.6 | c.7878G>A | p.Leu2626= | synonymous_variant, NMD_transcript_variant | 49/80 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000681 AC: 17AN: 249730Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135118
GnomAD4 exome AF: 0.0000199 AC: 29AN: 1459470Hom.: 0 Cov.: 37 AF XY: 0.0000193 AC XY: 14AN XY: 726144
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74290
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 17, 2018 | - - |
RYR1-Related Disorders Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at