Variant rs199849275 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000540.3(RYR1):c.7836-28dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,600,600 control chromosomes in the GnomAD database, including 267 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 14 hom., cov: 29)

Exomes 𝑓: 0.014 ( 253 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.62

Variant links:

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]

RYR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 19-38502851-G-GA is Benign according to our data. Variant chr19-38502851-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 256561.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0109 (1653/151022) while in subpopulation NFE AF= 0.0172 (1162/67616). AF 95% confidence interval is 0.0164. There are 14 homozygotes in gnomad4. There are 751 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3 linkuse as main transcript	c.7836-28dup		intron_variant		ENST00000359596.8	NP_000531.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8 linkuse as main transcript	c.7836-28dup	intron_variant	5	NM_000540.3	ENSP00000352608	A2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.7836-28dup	intron_variant	1		ENSP00000347667	P4	P21817-2
RYR1	ENST00000594335.5 linkuse as main transcript	c.1288-28dup	intron_variant, NMD_transcript_variant	1		ENSP00000470927
RYR1	ENST00000599547.6 linkuse as main transcript	c.7836-28dup	intron_variant, NMD_transcript_variant	2		ENSP00000471601

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1653

AN:

150908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00312

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.000391

Gnomad SAS

AF:

0.00337

Gnomad FIN

AF:

0.00803

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0111

GnomAD3 exomes

AF:

0.00918

AC:

2221

AN:

241952

Hom.:

AF XY:

0.00950

AC XY:

1248

AN XY:

131360

show subpopulations

Gnomad AFR exome

AF:

0.00220

Gnomad AMR exome

AF:

0.00749

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.00624

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0128

GnomAD4 exome

AF:

0.0136

AC:

19697

AN:

1449578

Hom.:

253

Cov.:

AF XY:

0.0134

AC XY:

9658

AN XY:

721456

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.00944

Gnomad4 ASJ exome

AF:

0.0133

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00309

Gnomad4 FIN exome

AF:

0.00876

Gnomad4 NFE exome

AF:

0.0157

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0109

AC:

1653

AN:

151022

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

751

AN XY:

73756

show subpopulations

Gnomad4 AFR

AF:

0.00311

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.000392

Gnomad4 SAS

AF:

0.00358

Gnomad4 FIN

AF:

0.00803

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0110

Alfa

AF:

0.00759

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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