Variant chr19-38499270-C-T 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.7027+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00542 in 1,613,978 control chromosomes in the GnomAD database, including 235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 202 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.45

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=-0.91).

BP6

Variant 19-38499270-C-T is Benign according to our data. Variant chr19-38499270-C-T is described in ClinVar as [Benign]. Clinvar id is 133176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38499270-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0632 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.7027+27C>T		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.7027+27C>T	intron_variant	5	NM_000540.3	ENSP00000352608	A2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.7027+27C>T	intron_variant	1		ENSP00000347667	P4	P21817-2
RYR1	ENST00000594335.5 linkuse as main transcript	c.479+27C>T	intron_variant, NMD_transcript_variant	1		ENSP00000470927
RYR1	ENST00000599547.6 linkuse as main transcript	c.7027+27C>T	intron_variant, NMD_transcript_variant	2		ENSP00000471601

Frequencies

GnomAD3 genomes

AF:

0.00845

AC:

1285

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0691

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0138

AC:

3473

AN:

251142

Hom.:

AF XY:

0.0125

AC XY:

1694

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.0441

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.0603

Gnomad SAS exome

AF:

0.0215

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00898

GnomAD4 exome

AF:

0.00511

AC:

7468

AN:

1461740

Hom.:

202

Cov.:

AF XY:

0.00541

AC XY:

3936

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00388

Gnomad4 AMR exome

AF:

0.0412

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.0733

Gnomad4 SAS exome

AF:

0.0216

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.000172

Gnomad4 OTH exome

AF:

0.00757

GnomAD4 genome

AF:

0.00844

AC:

1285

AN:

152238

Hom.:

Cov.:

AF XY:

0.00999

AC XY:

744

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00429

Gnomad4 AMR

AF:

0.0371

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0691

Gnomad4 SAS

AF:

0.0269

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00334

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.0550

AC:

190

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	Leiden Muscular Dystrophy (RYR1)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.14

DANN

Benign

0.77

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