Variant 19-38506683-T-C 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_000540.3(RYR1):c.8692+137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,474,534 control chromosomes in the GnomAD database, including 60,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8631 hom., cov: 31)

Exomes 𝑓: 0.27 ( 51745 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.994

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=-0.87).

BP6

Variant 19-38506683-T-C is Benign according to our data. Variant chr19-38506683-T-C is described in ClinVar as [Benign]. Clinvar id is 590617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3 linkuse as main transcript	c.8692+137T>C		intron_variant		ENST00000359596.8	NP_000531.2	P21817-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RYR1	ENST00000359596.8 linkuse as main transcript	c.8692+137T>C	intron_variant	5	NM_000540.3	ENSP00000352608.2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.8692+137T>C	intron_variant	1		ENSP00000347667.3	P21817-2
RYR1	ENST00000594335.5 linkuse as main transcript	n.2143+137T>C	intron_variant	1		ENSP00000470927.2	M0R014
RYR1	ENST00000599547.6 linkuse as main transcript	n.8692+137T>C	intron_variant	2		ENSP00000471601.2	M0R127

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49473

AN:

151858

Hom.:

8595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.430

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.363

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.271

AC:

358585

AN:

1322558

Hom.:

51745

Cov.:

AF XY:

0.276

AC XY:

182048

AN XY:

659430

show subpopulations

Gnomad4 AFR exome

AF:

0.428

Gnomad4 AMR exome

AF:

0.380

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.334

Gnomad4 SAS exome

AF:

0.444

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.326

AC:

49570

AN:

151976

Hom.:

8631

Cov.:

AF XY:

0.333

AC XY:

24768

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.431

Gnomad4 AMR

AF:

0.355

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.289

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.156

Hom.:

277

Bravo

AF:

0.333

Asia WGS

AF:

0.488

AC:

1694

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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 specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.4

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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