19-38559839-G-C

Position:

• chr19-38559839-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000540.3(RYR1):​c.12283-1274G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 151,992 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.052 (253 hom., cov: 30)
• Consequence: RYR1 NM_000540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR1	NM_000540.3	c.12283-1274G>C		intron_variant		ENST00000359596.8	NP_000531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR1	ENST00000359596.8	c.12283-1274G>C		intron_variant		5	NM_000540.3	ENSP00000352608.2

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7848 AN: 151878 Hom.: 253 Cov.: 30

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0513

Gnomad OTH AF: 0.0622

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0517 AC: 7855 AN: 151992 Hom.: 253 Cov.: 30 AF XY: 0.0554 AC XY: 4116 AN XY: 74262

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.0532

Gnomad4 ASJ AF: 0.0809

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0351

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0513

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0226 Hom.: 18

Bravo AF: 0.0479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.054
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs12327672; hg19: chr19-39050479;