rs12459087

Variant names:

• chr19-47466137-G-A
• rs12459087
• NM_015063.3:c.267C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-47466137-G-A
• chr19-47466137-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_015063.3(SLC8A2):​c.267C>T​(p.Ile89Ile) 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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015063.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A2	NM_015063.3	MANE Select	c.267C>T	p.Ile89Ile	synonymous	Exon 2 of 10	NP_055878.1	Q9UPR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A2	ENST00000236877.11	TSL:1 MANE Select	c.267C>T	p.Ile89Ile	synonymous	Exon 2 of 10	ENSP00000236877.5	Q9UPR5
	SLC8A2	ENST00000594353.1	TSL:4	c.-13C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000472233.1	M0R211
	SLC8A2	ENST00000885652.1		c.267C>T	p.Ile89Ile	synonymous	Exon 2 of 9	ENSP00000555711.1

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

GnomAD2 exomes AF: 0.0898 AC: 22562 AN: 251378 AF XY: 0.0934

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 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

African (AFR) AF: 0.0159 AC: 534 AN: 33480

American (AMR) AF: 0.0470 AC: 2101 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0584 AC: 1526 AN: 26136

East Asian (EAS) AF: 0.0505 AC: 2003 AN: 39700

South Asian (SAS) AF: 0.109 AC: 9392 AN: 86258

European-Finnish (FIN) AF: 0.109 AC: 5813 AN: 53408

Middle Eastern (MID) AF: 0.0550 AC: 317 AN: 5768

European-Non Finnish (NFE) AF: 0.112 AC: 124766 AN: 1111976

Other (OTH) AF: 0.0947 AC: 5721 AN: 60396

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

African (AFR) AF: 0.0193 AC: 804 AN: 41572

American (AMR) AF: 0.0626 AC: 958 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3470

East Asian (EAS) AF: 0.0644 AC: 334 AN: 5186

South Asian (SAS) AF: 0.108 AC: 523 AN: 4824

European-Finnish (FIN) AF: 0.105 AC: 1118 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7409 AN: 68002

Other (OTH) AF: 0.0629 AC: 133 AN: 2116

Alfa AF: 0.0963 Hom.: 1647

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.3
DANN	Benign	0.88
PhyloP100		-0.42
Mutation Taster		=89/11	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: rs12459087; hg19: chr19-47969394; COSMIC: COSV52641741;