rs830142

Positions:

• chr19-47446095-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
SLC8A2	NM_015063.3	c.1763+1714C>T		intron_variant		ENST00000236877.11	NP_055878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A2	ENST00000236877.11	c.1763+1714C>T		intron_variant		1	NM_015063.3	ENSP00000236877	P1
SLC8A2	ENST00000542837.2	c.1031+1714C>T		intron_variant		2		ENSP00000437536
SLC8A2	ENST00000539381.5	n.254+1714C>T		intron_variant, non_coding_transcript_variant		2
SLC8A2	ENST00000601757.1	n.189+1339C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0602

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0552 Hom.: 121

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

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: rs830142; hg19: chr19-47949352;