rs10158497

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001035.3(RYR2):​c.49-6453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,528 control chromosomes in the GnomAD database, including 7,380 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 7380 hom., cov: 30)

Consequence

RYR2
NM_001035.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.284
Variant links:
Genes affected
RYR2 (HGNC:10484): (ryanodine receptor 2) This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RYR2NM_001035.3 linkuse as main transcriptc.49-6453A>G intron_variant ENST00000366574.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RYR2ENST00000366574.7 linkuse as main transcriptc.49-6453A>G intron_variant 1 NM_001035.3 P1Q92736-1
RYR2ENST00000659194.3 linkuse as main transcriptc.49-6453A>G intron_variant
RYR2ENST00000660292.2 linkuse as main transcriptc.49-6453A>G intron_variant
RYR2ENST00000609119.2 linkuse as main transcriptc.49-6453A>G intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.295
AC:
44630
AN:
151408
Hom.:
7363
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.446
Gnomad AMI
AF:
0.196
Gnomad AMR
AF:
0.181
Gnomad ASJ
AF:
0.256
Gnomad EAS
AF:
0.229
Gnomad SAS
AF:
0.277
Gnomad FIN
AF:
0.247
Gnomad MID
AF:
0.295
Gnomad NFE
AF:
0.246
Gnomad OTH
AF:
0.268
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.295
AC:
44683
AN:
151528
Hom.:
7380
Cov.:
30
AF XY:
0.294
AC XY:
21746
AN XY:
74056
show subpopulations
Gnomad4 AFR
AF:
0.446
Gnomad4 AMR
AF:
0.181
Gnomad4 ASJ
AF:
0.256
Gnomad4 EAS
AF:
0.228
Gnomad4 SAS
AF:
0.277
Gnomad4 FIN
AF:
0.247
Gnomad4 NFE
AF:
0.246
Gnomad4 OTH
AF:
0.275
Alfa
AF:
0.272
Hom.:
1803
Bravo
AF:
0.295
Asia WGS
AF:
0.245
AC:
849
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
6.2
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10158497; hg19: chr1-237427344; COSMIC: COSV63672825; API