rs830142

Variant names:

• chr19-47446095-G-A
• rs830142
• NM_015063.3:c.1763+1714C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015063.3(SLC8A2):​c.1763+1714C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 152,282 control chromosomes in the GnomAD database, including 175 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 0.043 (175 hom., cov: 31)
• Consequence: SLC8A2 NM_015063.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A2	NM_015063.3	c.1763+1714C>T		intron_variant	Intron 4 of 9	ENST00000236877.11	NP_055878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A2	ENST00000236877.11	c.1763+1714C>T		intron_variant	Intron 4 of 9	1	NM_015063.3	ENSP00000236877.5
SLC8A2	ENST00000542837.2	c.1031+1714C>T		intron_variant	Intron 3 of 8	2		ENSP00000437536.1
SLC8A2	ENST00000539381.5	n.254+1714C>T		intron_variant	Intron 2 of 7	2
SLC8A2	ENST00000601757.1	n.189+1339C>T		intron_variant	Intron 1 of 5	4

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6625 AN: 152164 Hom.: 175 Cov.: 31

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0601

Gnomad OTH AF: 0.0468

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

GnomAD4 genome AF: 0.0435 AC: 6620 AN: 152282 Hom.: 175 Cov.: 31 AF XY: 0.0416 AC XY: 3095 AN XY: 74468

African (AFR) AF: 0.0178 AC: 740 AN: 41576

American (AMR) AF: 0.0313 AC: 479 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3468

East Asian (EAS) AF: 0.128 AC: 660 AN: 5164

South Asian (SAS) AF: 0.0261 AC: 126 AN: 4824

European-Finnish (FIN) AF: 0.0291 AC: 309 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0602 AC: 4092 AN: 68008

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0485 Hom.: 176

Bravo AF: 0.0434

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.68
PhyloP100		0.26
Mutation Taster		=100/0	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: rs830142; hg19: chr19-47949352;