rs1469699
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000540.3(RYR1):c.7926+28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,598,578 control chromosomes in the GnomAD database, including 72,920 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.35 ( 10022 hom., cov: 31)
Exomes 𝑓: 0.29 ( 62898 hom. )
Consequence
RYR1
NM_000540.3 intron
NM_000540.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.51
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 19-38502998-A-G is Benign according to our data. Variant chr19-38502998-A-G is described in ClinVar as [Benign]. Clinvar id is 133216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38502998-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR1 | NM_000540.3 | c.7926+28A>G | intron_variant | ENST00000359596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR1 | ENST00000359596.8 | c.7926+28A>G | intron_variant | 5 | NM_000540.3 | A2 | |||
RYR1 | ENST00000355481.8 | c.7926+28A>G | intron_variant | 1 | P4 | ||||
RYR1 | ENST00000594335.5 | c.1378+28A>G | intron_variant, NMD_transcript_variant | 1 | |||||
RYR1 | ENST00000599547.6 | c.7926+28A>G | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.349 AC: 52935AN: 151798Hom.: 9983 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
52935
AN:
151798
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.337 AC: 81492AN: 241472Hom.: 14720 AF XY: 0.335 AC XY: 43861AN XY: 131100
GnomAD3 exomes
AF:
AC:
81492
AN:
241472
Hom.:
AF XY:
AC XY:
43861
AN XY:
131100
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.287 AC: 414744AN: 1446662Hom.: 62898 Cov.: 34 AF XY: 0.291 AC XY: 209244AN XY: 720132
GnomAD4 exome
AF:
AC:
414744
AN:
1446662
Hom.:
Cov.:
34
AF XY:
AC XY:
209244
AN XY:
720132
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.349 AC: 53037AN: 151916Hom.: 10022 Cov.: 31 AF XY: 0.356 AC XY: 26451AN XY: 74264
GnomAD4 genome
?
AF:
AC:
53037
AN:
151916
Hom.:
Cov.:
31
AF XY:
AC XY:
26451
AN XY:
74264
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1709
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:5Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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, no classification provided | literature only | Leiden Muscular Dystrophy (RYR1) | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 25, 2013 | - - |
Congenital multicore myopathy with external ophthalmoplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Central core myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
King Denborough syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at