rs147587000
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000540.3(RYR1):c.7860G>A(p.Gln2620Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,611,824 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00073 ( 1 hom., cov: 29)
Exomes 𝑓: 0.000098 ( 0 hom. )
Consequence
RYR1
NM_000540.3 synonymous
NM_000540.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.686
Genes affected
RYR1 (HGNC:10483): (ryanodine receptor 1) This gene encodes a ryanodine receptor found in skeletal muscle. The encoded protein functions as a calcium release channel in the sarcoplasmic reticulum but also serves to connect the sarcoplasmic reticulum and transverse tubule. Mutations in this gene are associated with malignant hyperthermia susceptibility, central core disease, and minicore myopathy with external ophthalmoplegia. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 19-38502904-G-A is Benign according to our data. Variant chr19-38502904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.686 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.7860G>A | p.Gln2620Gln | synonymous_variant | 49/106 | ENST00000359596.8 | NP_000531.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.7860G>A | p.Gln2620Gln | synonymous_variant | 49/106 | 5 | NM_000540.3 | ENSP00000352608.2 | ||
RYR1 | ENST00000355481.8 | c.7860G>A | p.Gln2620Gln | synonymous_variant | 49/105 | 1 | ENSP00000347667.3 | |||
RYR1 | ENST00000594335.5 | n.1311G>A | non_coding_transcript_exon_variant | 10/49 | 1 | ENSP00000470927.2 | ||||
RYR1 | ENST00000599547.6 | n.7860G>A | non_coding_transcript_exon_variant | 49/80 | 2 | ENSP00000471601.2 |
Frequencies
GnomAD3 genomes AF: 0.000730 AC: 111AN: 152054Hom.: 1 Cov.: 29
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GnomAD3 exomes AF: 0.000172 AC: 43AN: 249838Hom.: 0 AF XY: 0.000163 AC XY: 22AN XY: 135148
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GnomAD4 exome AF: 0.0000980 AC: 143AN: 1459652Hom.: 0 Cov.: 34 AF XY: 0.000109 AC XY: 79AN XY: 726202
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GnomAD4 genome AF: 0.000729 AC: 111AN: 152172Hom.: 1 Cov.: 29 AF XY: 0.000686 AC XY: 51AN XY: 74388
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 20, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
RYR1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | RYR1: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at