rs1495280

Positions:

• chr15-33635563-C-T

Variant summary

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

The NM_001036.6(RYR3):​c.3176-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,405,366 control chromosomes in the GnomAD database, including 168,667 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 0.52 (20673 hom., cov: 32)
  • Exomes 𝑓: 0.48 (147994 hom.)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

Genes affected

RYR3 (HGNC:10485): (ryanodine receptor 3) The protein encoded by this gene is a ryanodine receptor, which functions to release calcium from intracellular storage for use in many cellular processes. For example, the encoded protein is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

RYR3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6	c.3176-51C>T		intron_variant		ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.3176-51C>T		intron_variant		1	NM_001036.6	ENSP00000489262.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78409 AN: 151960 Hom.: 20631 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.483 AC: 605084 AN: 1253288 Hom.: 147994 Cov.: 17 AF XY: 0.482 AC XY: 303680 AN XY: 629734

Gnomad4 AFR exome AF: 0.586

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.489

GnomAD4 genome AF: 0.516 AC: 78512 AN: 152078 Hom.: 20673 Cov.: 32 AF XY: 0.518 AC XY: 38514 AN XY: 74344

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.490

Alfa AF: 0.461 Hom.: 26734

Bravo AF: 0.523

Asia WGS AF: 0.622 AC: 2162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.3
DANN	Benign	0.60

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: rs1495280; hg19: chr15-33927764;