Variant 19-38512513-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.9472+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 1,598,026 control chromosomes in the GnomAD database, including 3,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 281 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3464 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.49

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=-0.95).

BP6

Variant 19-38512513-C-T is Benign according to our data. Variant chr19-38512513-C-T is described in ClinVar as [Benign]. Clinvar id is 256583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 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.9472+30C>T		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.9472+30C>T	intron_variant	5	NM_000540.3	ENSP00000352608.2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.9472+30C>T	intron_variant	1		ENSP00000347667.3	P21817-2
RYR1	ENST00000594335.5 linkuse as main transcript	n.*215+30C>T	intron_variant	1		ENSP00000470927.2	M0R014
RYR1	ENST00000599547.6 linkuse as main transcript	n.*231+30C>T	intron_variant	2		ENSP00000471601.2	M0R127

Frequencies

GnomAD3 genomes

AF:

0.0550

AC:

8366

AN:

152176

Hom.:

281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0341

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0474

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.00635

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0857

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0639

Gnomad OTH

AF:

0.0630

GnomAD3 exomes

AF:

0.0671

AC:

16140

AN:

240568

Hom.:

659

AF XY:

0.0699

AC XY:

9181

AN XY:

131272

show subpopulations

Gnomad AFR exome

AF:

0.0314

Gnomad AMR exome

AF:

0.0711

Gnomad ASJ exome

AF:

0.0478

Gnomad EAS exome

AF:

0.00262

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0865

Gnomad NFE exome

AF:

0.0662

Gnomad OTH exome

AF:

0.0599

GnomAD4 exome

AF:

0.0660

AC:

95448

AN:

1445732

Hom.:

3464

Cov.:

AF XY:

0.0678

AC XY:

48781

AN XY:

719978

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.0677

Gnomad4 ASJ exome

AF:

0.0504

Gnomad4 EAS exome

AF:

0.0123

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0812

Gnomad4 NFE exome

AF:

0.0648

Gnomad4 OTH exome

AF:

0.0606

GnomAD4 genome

AF:

0.0550

AC:

8372

AN:

152294

Hom.:

281

Cov.:

AF XY:

0.0568

AC XY:

4227

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0341

Gnomad4 AMR

AF:

0.0476

Gnomad4 ASJ

AF:

0.0579

Gnomad4 EAS

AF:

0.00637

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.0857

Gnomad4 NFE

AF:

0.0639

Gnomad4 OTH

AF:

0.0633

Alfa

AF:

0.0577

Hom.:

Bravo

AF:

0.0501

Asia WGS

AF:

0.0690

AC:

240

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 28, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.019

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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