rs17765376

chr14-70148905-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SLC8A3	NM_182932.3	c.1784+17734G>A		intron_variant		ENST00000356921.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC8A3	ENST00000356921.7	c.1784+17734G>A		intron_variant		1	NM_182932.3	A1

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

Gnomad4 AFR AF: 0.0920

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.0377

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.195

Alfa AF: 0.213 Hom.: 5961

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

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: rs17765376; hg19: chr14-70615622;