rs7259674

Variant names:

• chr19-47432315-G-A
• rs7259674
• NM_015063.3:c.2241C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-47432315-G-A
• chr19-47432315-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015063.3(SLC8A2):​c.2241C>T​(p.His747His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,776 control chromosomes in the GnomAD database, including 11,449 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 0.10 (863 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10586 hom.)
• Consequence: SLC8A2 NM_015063.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 12 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A2	NM_015063.3	c.2241C>T	p.His747His	synonymous_variant	Exon 9 of 10	ENST00000236877.11	NP_055878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A2	ENST00000236877.11	c.2241C>T	p.His747His	synonymous_variant	Exon 9 of 10	1	NM_015063.3	ENSP00000236877.5

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15555 AN: 152094 Hom.: 867 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0752

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.104 AC: 26059 AN: 251152 AF XY: 0.104

Gnomad AFR exome AF: 0.0691

Gnomad AMR exome AF: 0.0630

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.129

Gnomad FIN exome AF: 0.0921

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.117 AC: 171279 AN: 1461564 Hom.: 10586 Cov.: 33 AF XY: 0.116 AC XY: 84176 AN XY: 727100

African (AFR) AF: 0.0723 AC: 2420 AN: 33466

American (AMR) AF: 0.0655 AC: 2929 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3930 AN: 26120

East Asian (EAS) AF: 0.116 AC: 4588 AN: 39686

South Asian (SAS) AF: 0.0519 AC: 4476 AN: 86230

European-Finnish (FIN) AF: 0.0960 AC: 5124 AN: 53400

Middle Eastern (MID) AF: 0.131 AC: 755 AN: 5766

European-Non Finnish (NFE) AF: 0.126 AC: 139716 AN: 1111808

Other (OTH) AF: 0.122 AC: 7341 AN: 60380

GnomAD4 genome AF: 0.102 AC: 15548 AN: 152212 Hom.: 863 Cov.: 32 AF XY: 0.0993 AC XY: 7392 AN XY: 74404

African (AFR) AF: 0.0708 AC: 2939 AN: 41532

American (AMR) AF: 0.0751 AC: 1148 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3470

East Asian (EAS) AF: 0.126 AC: 650 AN: 5168

South Asian (SAS) AF: 0.0479 AC: 231 AN: 4822

European-Finnish (FIN) AF: 0.0943 AC: 1000 AN: 10602

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8578 AN: 68006

Other (OTH) AF: 0.124 AC: 262 AN: 2110

Alfa AF: 0.111 Hom.: 525

Bravo AF: 0.102

EpiCase AF: 0.124

EpiControl AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-1.5
Mutation Taster		=97/3	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: rs7259674; hg19: chr19-47935572; COSMIC: COSV52638561; COSMIC: COSV52638561;