rs2278309

Positions:

• chr15-33750626-T-C

Variant summary

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

The NM_001036.6(RYR3):​c.8399+340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,178 control chromosomes in the GnomAD database, including 49,580 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 0.81 (49580 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.8399+340T>C		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.8399+340T>C		intron_variant		1	NM_001036.6	P4

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122637 AN: 152060 Hom.: 49548 Cov.: 33

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.806 AC: 122728 AN: 152178 Hom.: 49580 Cov.: 33 AF XY: 0.806 AC XY: 59982 AN XY: 74398

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.793

Alfa AF: 0.798 Hom.: 27927

Bravo AF: 0.813

Asia WGS AF: 0.709 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.51

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: rs2278309; hg19: chr15-34042827;