Variant 19-38444726-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.631+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 1,416,604 control chromosomes in the GnomAD database, including 1,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 314 hom., cov: 28)

Exomes 𝑓: 0.044 ( 1526 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0210

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=-0.83).

BP6

Variant 19-38444726-C-T is Benign according to our data. Variant chr19-38444726-C-T is described in ClinVar as [Benign]. Clinvar id is 256532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38444726-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0786 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.631+49C>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.631+49C>T	intron_variant	5	NM_000540.3	ENSP00000352608	A2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.631+49C>T	intron_variant	1		ENSP00000347667	P4	P21817-2
RYR1	ENST00000599547.6 linkuse as main transcript	c.631+49C>T	intron_variant, NMD_transcript_variant	2		ENSP00000471601

Frequencies

GnomAD3 genomes

AF:

0.0564

AC:

8537

AN:

151394

Hom.:

315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0806

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.0990

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.0511

Gnomad FIN

AF:

0.0954

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.0426

Gnomad OTH

AF:

0.0576

GnomAD3 exomes

AF:

0.0516

AC:

10330

AN:

200180

Hom.:

363

AF XY:

0.0521

AC XY:

5630

AN XY:

108060

show subpopulations

Gnomad AFR exome

AF:

0.0857

Gnomad AMR exome

AF:

0.0243

Gnomad ASJ exome

AF:

0.0964

Gnomad EAS exome

AF:

0.0157

Gnomad SAS exome

AF:

0.0549

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.0458

Gnomad OTH exome

AF:

0.0538

GnomAD4 exome

AF:

0.0438

AC:

55415

AN:

1265092

Hom.:

1526

Cov.:

AF XY:

0.0446

AC XY:

28342

AN XY:

635012

show subpopulations

Gnomad4 AFR exome

AF:

0.0905

Gnomad4 AMR exome

AF:

0.0253

Gnomad4 ASJ exome

AF:

0.0999

Gnomad4 EAS exome

AF:

0.00837

Gnomad4 SAS exome

AF:

0.0530

Gnomad4 FIN exome

AF:

0.0926

Gnomad4 NFE exome

AF:

0.0391

Gnomad4 OTH exome

AF:

0.0490

GnomAD4 genome

AF:

0.0564

AC:

8552

AN:

151512

Hom.:

314

Cov.:

AF XY:

0.0587

AC XY:

4345

AN XY:

73972

show subpopulations

Gnomad4 AFR

AF:

0.0808

Gnomad4 AMR

AF:

0.0303

Gnomad4 ASJ

AF:

0.0990

Gnomad4 EAS

AF:

0.0148

Gnomad4 SAS

AF:

0.0509

Gnomad4 FIN

AF:

0.0954

Gnomad4 NFE

AF:

0.0426

Gnomad4 OTH

AF:

0.0570

Alfa

AF:

0.0513

Hom.:

118

Bravo

AF:

0.0530

Asia WGS

AF:

0.0340

AC:

117

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 26, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

DANN

Benign

0.70

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