rs965471

chr15-33788936-G-Achr15-33788936-G-Cchr15-33788936-G-T

Variant summary

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

The NM_001036.6(RYR3):c.9830+478G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,022 control chromosomes in the GnomAD database, including 29,721 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 0.61 (29721 hom., cov: 32)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.9830+478G>A		intron_variant		ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.9830+478G>A		intron_variant		1	NM_001036.6	P4

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93235 AN: 151904 Hom.: 29718 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.614 AC: 93281 AN: 152022 Hom.: 29721 Cov.: 32 AF XY: 0.622 AC XY: 46237 AN XY: 74326

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.647

Alfa AF: 0.646 Hom.: 8940

Bravo AF: 0.589

Asia WGS AF: 0.856 AC: 2975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.4
Dann	Benign	0.40

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: rs965471; hg19: chr15-34081137;