rs12459087

Positions:

• chr19-47466137-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_015063.3(SLC8A2):​c.267C>T​(p.Ile89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,614,138 control chromosomes in the GnomAD database, including 9,127 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 0.076 (595 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8532 hom.)
• Consequence: SLC8A2 NM_015063.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

Genes affected

SLC8A2 (HGNC:11069): (solute carrier family 8 member A2) Predicted to enable calcium:cation antiporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration and calcium:sodium antiporter activity. Predicted to be involved in several processes, including inorganic cation transmembrane transport; learning or memory; and regulation of short-term neuronal synaptic plasticity. Predicted to act upstream of or within several processes, including modulation of chemical synaptic transmission; regulation of action potential firing pattern; and response to ischemia. Part of presynapse. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-0.424 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC8A2	NM_015063.3	c.267C>T	p.Ile89=	synonymous_variant	2/10	ENST00000236877.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC8A2	ENST00000236877.11	c.267C>T	p.Ile89=	synonymous_variant	2/10	1	NM_015063.3	P1

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11648 AN: 152174 Hom.: 595 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0627

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0635

GnomAD3 exomes AF: 0.0898 AC: 22562 AN: 251378 Hom.: 1193 AF XY: 0.0934 AC XY: 12688 AN XY: 135898

Gnomad AFR exome AF: 0.0172

Gnomad AMR exome AF: 0.0451

Gnomad ASJ exome AF: 0.0579

Gnomad EAS exome AF: 0.0723

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.0850

GnomAD4 exome AF: 0.104 AC: 152173 AN: 1461846 Hom.: 8532 Cov.: 34 AF XY: 0.104 AC XY: 75738 AN XY: 727226

Gnomad4 AFR exome AF: 0.0159

Gnomad4 AMR exome AF: 0.0470

Gnomad4 ASJ exome AF: 0.0584

Gnomad4 EAS exome AF: 0.0505

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.0947

GnomAD4 genome AF: 0.0765 AC: 11646 AN: 152292 Hom.: 595 Cov.: 32 AF XY: 0.0759 AC XY: 5651 AN XY: 74466

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.0626

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.0644

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0993 Hom.: 1337

Bravo AF: 0.0717

Asia WGS AF: 0.0920 AC: 323 AN: 3478

EpiCase AF: 0.101

EpiControl AF: 0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.3
DANN	Benign	0.88

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: rs12459087; hg19: chr19-47969394; COSMIC: COSV52641741;