ENST00000559457.2:n.220-937G>A

Variant names:

• chr15-33304875-C-T
• rs2676071
• ENST00000559457.2:n.220-937G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000559457.2(RYR3-DT):​n.220-937G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,054 control chromosomes in the GnomAD database, including 32,006 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 0.64 (32006 hom., cov: 32)
• Consequence: RYR3-DT ENST00000559457.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 7 publications found

Genes affected

RYR3-DT (HGNC:51417): (RYR3 divergent transcript)

ENSG00000293377 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3-DT	NR_120326.1	n.197-937G>A		intron_variant	Intron 2 of 2
RYR3-DT	NR_120327.1	n.183-937G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR3-DT	ENST00000559457.2	n.220-937G>A		intron_variant	Intron 2 of 2	3
RYR3-DT	ENST00000561458.6	n.507-937G>A		intron_variant	Intron 2 of 2	2
RYR3-DT	ENST00000653439.2	n.339+5275G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97810 AN: 151936 Hom.: 31988 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.644 AC: 97870 AN: 152054 Hom.: 32006 Cov.: 32 AF XY: 0.644 AC XY: 47867 AN XY: 74300

African (AFR) AF: 0.752 AC: 31204 AN: 41488

American (AMR) AF: 0.559 AC: 8534 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2144 AN: 3470

East Asian (EAS) AF: 0.596 AC: 3085 AN: 5172

South Asian (SAS) AF: 0.632 AC: 3041 AN: 4814

European-Finnish (FIN) AF: 0.631 AC: 6659 AN: 10546

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41151 AN: 67978

Other (OTH) AF: 0.644 AC: 1360 AN: 2112

Alfa AF: 0.621 Hom.: 21403

Bravo AF: 0.644

Asia WGS AF: 0.632 AC: 2200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.42
PhyloP100		-0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2676071; hg19: chr15-33597076;