19-47430471-A-G

Variant names:

• chr19-47430471-A-G
• rs8104926
• NM_015063.3:c.2390-6T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015063.3(SLC8A2):​c.2390-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 1,597,108 control chromosomes in the GnomAD database, including 625,195 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (45747 hom., cov: 34)
  • Exomes 𝑓: 0.89 (579448 hom.)
• Consequence: SLC8A2 NM_015063.3 splice_region, intron
• Scores: Splicing: ADA: 0.00007330
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.411
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-47430471-A-G is Benign according to our data. Variant chr19-47430471-A-G is described in ClinVar as Benign. ClinVar VariationId is 1265253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.909 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A2	NM_015063.3	MANE Select	c.2390-6T>C		splice_region intron	N/A	NP_055878.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A2	ENST00000236877.11	TSL:1 MANE Select	c.2390-6T>C		splice_region intron	N/A	ENSP00000236877.5
	SLC8A2	ENST00000542837.2	TSL:2	c.1658-6T>C		splice_region intron	N/A	ENSP00000437536.1
	SLC8A2	ENST00000539381.5	TSL:2	n.881-6T>C		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111351 AN: 152102 Hom.: 45751 Cov.: 34

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.791

GnomAD2 exomes AF: 0.843 AC: 186918 AN: 221726 AF XY: 0.853

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.840

Gnomad ASJ exome AF: 0.947

Gnomad EAS exome AF: 0.825

Gnomad FIN exome AF: 0.885

Gnomad NFE exome AF: 0.914

Gnomad OTH exome AF: 0.876

GnomAD4 exome AF: 0.890 AC: 1286109 AN: 1444888 Hom.: 579448 Cov.: 56 AF XY: 0.890 AC XY: 639425 AN XY: 718464

African (AFR) AF: 0.303 AC: 10064 AN: 33256

American (AMR) AF: 0.834 AC: 36524 AN: 43780

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 24323 AN: 25718

East Asian (EAS) AF: 0.870 AC: 34238 AN: 39338

South Asian (SAS) AF: 0.812 AC: 68975 AN: 84980

European-Finnish (FIN) AF: 0.892 AC: 40457 AN: 45336

Middle Eastern (MID) AF: 0.876 AC: 4659 AN: 5320

European-Non Finnish (NFE) AF: 0.917 AC: 1015368 AN: 1107390

Other (OTH) AF: 0.862 AC: 51501 AN: 59770

GnomAD4 genome AF: 0.731 AC: 111345 AN: 152220 Hom.: 45747 Cov.: 34 AF XY: 0.734 AC XY: 54632 AN XY: 74440

African (AFR) AF: 0.326 AC: 13523 AN: 41510

American (AMR) AF: 0.780 AC: 11933 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3285 AN: 3472

East Asian (EAS) AF: 0.832 AC: 4305 AN: 5172

South Asian (SAS) AF: 0.809 AC: 3905 AN: 4828

European-Finnish (FIN) AF: 0.896 AC: 9511 AN: 10620

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62203 AN: 68008

Other (OTH) AF: 0.790 AC: 1670 AN: 2114

Alfa AF: 0.830 Hom.: 17874

Bravo AF: 0.708

Asia WGS AF: 0.793 AC: 2760 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Apr 26, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.7
DANN	Benign	0.69
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000073
dbscSNV1_RF	Benign	0.0040
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: rs8104926; hg19: chr19-47933728;