Variant 1-237591040-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001035.3(RYR2):c.4160+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,388,112 control chromosomes in the GnomAD database, including 157,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12981 hom., cov: 28)

Exomes 𝑓: 0.46 ( 144603 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0570

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]

RYR2 links:

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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=-0.91).

BP6

Variant 1-237591040-A-G is Benign according to our data. Variant chr1-237591040-A-G is described in ClinVar as [Benign]. Clinvar id is 257210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3 linkuse as main transcript	c.4160+48A>G		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.4160+48A>G	intron_variant	1	NM_001035.3	P1	Q92736-1
RYR2	ENST00000659194.3 linkuse as main transcript	c.4160+48A>G	intron_variant
RYR2	ENST00000660292.2 linkuse as main transcript	c.4160+48A>G	intron_variant
RYR2	ENST00000609119.2 linkuse as main transcript	c.4160+48A>G	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

57963

AN:

147794

Hom.:

12979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.326

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.419

GnomAD3 exomes

AF:

0.453

AC:

81083

AN:

178926

Hom.:

19378

AF XY:

0.449

AC XY:

42693

AN XY:

94984

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.610

Gnomad ASJ exome

AF:

0.484

Gnomad EAS exome

AF:

0.311

Gnomad SAS exome

AF:

0.349

Gnomad FIN exome

AF:

0.507

Gnomad NFE exome

AF:

0.480

Gnomad OTH exome

AF:

0.479

GnomAD4 exome

AF:

0.459

AC:

569495

AN:

1240214

Hom.:

144603

Cov.:

AF XY:

0.457

AC XY:

280967

AN XY:

614892

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.470

Gnomad4 EAS exome

AF:

0.347

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.501

Gnomad4 NFE exome

AF:

0.477

Gnomad4 OTH exome

AF:

0.435

GnomAD4 genome

AF:

0.392

AC:

57958

AN:

147898

Hom.:

12981

Cov.:

AF XY:

0.391

AC XY:

28081

AN XY:

71764

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.497

Gnomad4 ASJ

AF:

0.469

Gnomad4 EAS

AF:

0.315

Gnomad4 SAS

AF:

0.326

Gnomad4 FIN

AF:

0.485

Gnomad4 NFE

AF:

0.483

Gnomad4 OTH

AF:

0.414

Alfa

AF:

0.459

Hom.:

11631

Bravo

AF:

0.395

Asia WGS

AF:

0.286

AC:

959

AN:

3352

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

DANN

Benign

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over