rs4238566

Variant names:

• chr15-33615427-A-C
• rs4238566
• NM_001036.6:c.2357+2052A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-33615427-A-C
• chr15-33615427-A-G

Variant summary

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

The NM_001036.6(RYR3):​c.2357+2052A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,108 control chromosomes in the GnomAD database, including 33,151 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 0.65 (33151 hom., cov: 33)
• Consequence: RYR3 NM_001036.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6	c.2357+2052A>C		intron_variant	Intron 19 of 103	ENST00000634891.2	NP_001027.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2	c.2357+2052A>C		intron_variant	Intron 19 of 103	1	NM_001036.6	ENSP00000489262.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98392 AN: 151990 Hom.: 33144 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.647 AC: 98432 AN: 152108 Hom.: 33151 Cov.: 33 AF XY: 0.648 AC XY: 48182 AN XY: 74342

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.809

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.669

Alfa AF: 0.730 Hom.: 71728

Bravo AF: 0.632

Asia WGS AF: 0.532 AC: 1851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.17

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: rs4238566; hg19: chr15-33907628;