rs4952404

chr2-40333490-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021097.5(SLC8A1):c.1808+94983G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 149,990 control chromosomes in the GnomAD database, including 3,388 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 0.19 (3388 hom., cov: 31)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

Genes affected

SLC8A1 (HGNC:11068): (solute carrier family 8 member A1) In cardiac myocytes, Ca(2+) concentrations alternate between high levels during contraction and low levels during relaxation. The increase in Ca(2+) concentration during contraction is primarily due to release of Ca(2+) from intracellular stores. However, some Ca(2+) also enters the cell through the sarcolemma (plasma membrane). During relaxation, Ca(2+) is sequestered within the intracellular stores. To prevent overloading of intracellular stores, the Ca(2+) that entered across the sarcolemma must be extruded from the cell. The Na(+)-Ca(2+) exchanger is the primary mechanism by which the Ca(2+) is extruded from the cell during relaxation. In the heart, the exchanger may play a key role in digitalis action. The exchanger is the dominant mechanism in returning the cardiac myocyte to its resting state following excitation.[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC8A1	NM_021097.5	c.1808+94983G>A		intron_variant		ENST00000332839.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC8A1	ENST00000332839.9	c.1808+94983G>A		intron_variant		1	NM_021097.5	P4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28411 AN: 149916 Hom.: 3391 Cov.: 31

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.189 AC: 28407 AN: 149990 Hom.: 3388 Cov.: 31 AF XY: 0.197 AC XY: 14399 AN XY: 73096

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.212

Alfa AF: 0.221 Hom.: 5326

Bravo AF: 0.172

Asia WGS AF: 0.332 AC: 1152 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.73

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: rs4952404; hg19: chr2-40560630;