dbSNP rs7259674: SLC8A2:p.His747His (chr19-47432315-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

Variant links:

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]

SLC8A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.2241C>T	p.His747His	synonymous_variant	Exon 9 of 10	ENST00000236877.11	NP_055878.1	Q9UPR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A2	ENST00000236877.11 link	c.2241C>T	p.His747His	synonymous_variant	Exon 9 of 10	1	NM_015063.3	ENSP00000236877.5		Q9UPR5

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15555

AN:

152094

Hom.:

867

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.104

AC:

26059

AN:

251152

Hom.:

1526

AF XY:

0.104

AC XY:

14121

AN XY:

135784

show subpopulations

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 SAS exome

AF:

0.0528

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.:

AF XY:

0.116

AC XY:

84176

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.0723

Gnomad4 AMR exome

AF:

0.0655

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.0519

Gnomad4 FIN exome

AF:

0.0960

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.102

AC:

15548

AN:

152212

Hom.:

863

Cov.:

AF XY:

0.0993

AC XY:

7392

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0708

Gnomad4 AMR

AF:

0.0751

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.0479

Gnomad4 FIN

AF:

0.0943

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.124

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over