19-38442305-G-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000540.3(RYR1):c.166-44G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,300,852 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.021 ( 122 hom., cov: 30)
Exomes 𝑓: 0.0023 ( 74 hom. )
Consequence
RYR1
NM_000540.3 intron
NM_000540.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0640
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BP6
Variant 19-38442305-G-C is Benign according to our data. Variant chr19-38442305-G-C is described in ClinVar as [Benign]. Clinvar id is 256461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.166-44G>C | intron_variant | Intron 2 of 105 | 5 | NM_000540.3 | ENSP00000352608.2 | |||
RYR1 | ENST00000355481.8 | c.166-44G>C | intron_variant | Intron 2 of 104 | 1 | ENSP00000347667.3 | ||||
RYR1 | ENST00000599547.6 | n.166-44G>C | intron_variant | Intron 2 of 79 | 2 | ENSP00000471601.2 |
Frequencies
GnomAD3 genomes AF: 0.0206 AC: 3119AN: 151340Hom.: 121 Cov.: 30
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GnomAD3 exomes AF: 0.00566 AC: 1410AN: 248992Hom.: 56 AF XY: 0.00412 AC XY: 555AN XY: 134750
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GnomAD4 exome AF: 0.00231 AC: 2650AN: 1149398Hom.: 74 Cov.: 16 AF XY: 0.00194 AC XY: 1140AN XY: 586870
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GnomAD4 genome AF: 0.0206 AC: 3122AN: 151454Hom.: 122 Cov.: 30 AF XY: 0.0201 AC XY: 1486AN XY: 74036
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Jul 09, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not specified Benign:1
Oct 17, 2013
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at