14-70111982-A-G

Position:

• chr14-70111982-A-G

Variant summary

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

The NM_182932.3(SLC8A3):​c.1785-51043T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,048 control chromosomes in the GnomAD database, including 16,443 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 0.45 (16443 hom., cov: 32)
• Consequence: SLC8A3 NM_182932.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A3	NM_182932.3	c.1785-51043T>C		intron_variant		ENST00000356921.7	NP_891977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A3	ENST00000356921.7	c.1785-51043T>C		intron_variant		1	NM_182932.3	ENSP00000349392	A1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68868 AN: 151930 Hom.: 16430 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.453 AC: 68912 AN: 152048 Hom.: 16443 Cov.: 32 AF XY: 0.460 AC XY: 34223 AN XY: 74338

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.431

Alfa AF: 0.438 Hom.: 20294

Bravo AF: 0.453

Asia WGS AF: 0.789 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.50

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: rs1035717; hg19: chr14-70578699;