Variant 19-38452790-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_StrongBS1BS2

The NM_000540.3(RYR1):c.1245-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,550,576 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 13 hom., cov: 32)

Exomes 𝑓: 0.017 ( 249 hom. )

Consequence

RYR1
NM_000540.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0330

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=-0.81).

BP6

Variant 19-38452790-C-T is Benign according to our data. Variant chr19-38452790-C-T is described in ClinVar as [Benign]. Clinvar id is 256421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-38452790-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0126 (1920/152358) while in subpopulation NFE AF= 0.0192 (1309/68032). AF 95% confidence interval is 0.0184. There are 13 homozygotes in gnomad4. There are 918 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3 linkuse as main transcript	c.1245-29C>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.1245-29C>T	intron_variant	5	NM_000540.3	ENSP00000352608.2	P21817-1
RYR1	ENST00000355481.8 linkuse as main transcript	c.1245-29C>T	intron_variant	1		ENSP00000347667.3	P21817-2
RYR1	ENST00000599547.6 linkuse as main transcript	n.1245-29C>T	intron_variant	2		ENSP00000471601.2	M0R127

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1920

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00330

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0278

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0192

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.0124

AC:

1983

AN:

160528

Hom.:

AF XY:

0.0123

AC XY:

1065

AN XY:

86452

show subpopulations

Gnomad AFR exome

AF:

0.00341

Gnomad AMR exome

AF:

0.00351

Gnomad ASJ exome

AF:

0.00520

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00575

Gnomad FIN exome

AF:

0.0340

Gnomad NFE exome

AF:

0.0179

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.0171

AC:

23931

AN:

1398218

Hom.:

249

Cov.:

AF XY:

0.0168

AC XY:

11605

AN XY:

689478

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00459

Gnomad4 ASJ exome

AF:

0.00449

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00566

Gnomad4 FIN exome

AF:

0.0333

Gnomad4 NFE exome

AF:

0.0192

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.0126

AC:

1920

AN:

152358

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

918

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00329

Gnomad4 AMR

AF:

0.00810

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.0278

Gnomad4 NFE

AF:

0.0192

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00876

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.2

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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