rs2291734

chr15-33636299-G-A

Variant summary

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

The NM_001036.6(RYR3):c.3382-77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,266,648 control chromosomes in the GnomAD database, including 25,325 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 0.16 (2279 hom., cov: 32)
  • Exomes 𝑓: 0.20 (23046 hom.)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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]

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 (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.3382-77G>A		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.3382-77G>A		intron_variant		1	NM_001036.6	P4
RYR3	ENST00000389232.9	c.3382-77G>A		intron_variant		5		A1
RYR3	ENST00000415757.7	c.3382-77G>A		intron_variant		2		A2
RYR3	ENST00000634418.1	c.3382-77G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23627 AN: 151890 Hom.: 2274 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.198 AC: 220512 AN: 1114640 Hom.: 23046 AF XY: 0.199 AC XY: 113152 AN XY: 569870

Gnomad4 AFR exome AF: 0.0356

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.156 AC: 23652 AN: 152008 Hom.: 2279 Cov.: 32 AF XY: 0.159 AC XY: 11847 AN XY: 74300

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.151

Alfa AF: 0.185 Hom.: 5039

Bravo AF: 0.148

Asia WGS AF: 0.200 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.90
Dann	Benign	0.46

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: rs2291734; hg19: chr15-33928500; COSMIC: COSV66789928;