19-38512051-C-T

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.9173-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,609,982 control chromosomes in the GnomAD database, including 14,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2277 hom., cov: 32)

Exomes 𝑓: 0.12 ( 12095 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.783

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-38512051-C-T is Benign according to our data. Variant chr19-38512051-C-T is described in ClinVar as [Benign]. Clinvar id is 133238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38512051-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR1	NM_000540.3 link	c.9173-21C>T		intron_variant	Intron 61 of 105	ENST00000359596.8	NP_000531.2	P21817-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RYR1	ENST00000359596.8 link	c.9173-21C>T	intron_variant	Intron 61 of 105	5	NM_000540.3	ENSP00000352608.2	P21817-1
RYR1	ENST00000355481.8 link	c.9173-21C>T	intron_variant	Intron 61 of 104	1		ENSP00000347667.3	P21817-2
RYR1	ENST00000594335.5 link	n.2574-21C>T	intron_variant	Intron 21 of 48	1		ENSP00000470927.2	M0R014
RYR1	ENST00000599547.6 link	n.9173-194C>T	intron_variant	Intron 61 of 79	2		ENSP00000471601.2	M0R127

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23868

AN:

151982

Hom.:

2265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.0867

Gnomad EAS

AF:

0.0667

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.141

AC:

34763

AN:

246912

Hom.:

2988

AF XY:

0.136

AC XY:

18191

AN XY:

133582

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.0760

Gnomad EAS exome

AF:

0.0528

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.122

AC:

178235

AN:

1457882

Hom.:

12095

Cov.:

AF XY:

0.123

AC XY:

88846

AN XY:

725102

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.0809

Gnomad4 EAS exome

AF:

0.0831

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.157

AC:

23921

AN:

152100

Hom.:

2277

Cov.:

AF XY:

0.159

AC XY:

11816

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.0867

Gnomad4 EAS

AF:

0.0667

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.115

Hom.:

1189

Bravo

AF:

0.166

Asia WGS

AF:

0.149

AC:

518

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

RYR1 database

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

not specified

Benign:1

Oct 28, 2013

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.44

DANN

Benign

0.56

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