rs17765376

Variant names:

• chr14-70148905-C-T
• rs17765376
• NM_182932.3:c.1784+17734G>A

Variant summary

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

The NM_182932.3(SLC8A3):​c.1784+17734G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 146,220 control chromosomes in the GnomAD database, including 2,470 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 0.17 (2470 hom., cov: 31)
• Consequence: SLC8A3 NM_182932.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990
• Publications: 3 publications found

Genes affected

SLC8A3 (HGNC:11070): (solute carrier family 8 member A3) This gene encodes a member of the sodium/calcium exchanger integral membrane protein family. Na+/Ca2+ exchange proteins are involved in maintaining Ca2+ homeostasis in a wide variety of cell types. The protein is regulated by intracellular calcium ions and is found in both the plasma membrane and intracellular organellar membranes, where exchange of Na+ for Ca2+ occurs in an electrogenic manner. Alternative splicing has been observed for this gene and multiple variants have been described. [provided by RefSeq, Aug 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A3	NM_182932.3	c.1784+17734G>A		intron_variant	Intron 2 of 6	ENST00000356921.7	NP_891977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A3	ENST00000356921.7	c.1784+17734G>A		intron_variant	Intron 2 of 6	1	NM_182932.3	ENSP00000349392.3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 25075 AN: 146098 Hom.: 2472 Cov.: 31

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.171 AC: 25071 AN: 146220 Hom.: 2470 Cov.: 31 AF XY: 0.168 AC XY: 11977 AN XY: 71468

African (AFR) AF: 0.0920 AC: 3621 AN: 39348

American (AMR) AF: 0.155 AC: 2288 AN: 14778

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 868 AN: 3390

East Asian (EAS) AF: 0.0377 AC: 180 AN: 4776

South Asian (SAS) AF: 0.118 AC: 540 AN: 4560

European-Finnish (FIN) AF: 0.168 AC: 1732 AN: 10304

Middle Eastern (MID) AF: 0.246 AC: 64 AN: 260

European-Non Finnish (NFE) AF: 0.231 AC: 15205 AN: 65892

Other (OTH) AF: 0.195 AC: 396 AN: 2026

Alfa AF: 0.202 Hom.: 8917

Bravo AF: 0.158

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.3
DANN	Benign	0.40
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17765376; hg19: chr14-70615622;