rs2192773

Positions:

• chr2-40394610-T-A

Variant summary

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

The NM_021097.5(SLC8A1):​c.1808+33863A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 151,964 control chromosomes in the GnomAD database, including 41,710 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 0.73 (41710 hom., cov: 31)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1808+33863A>T		intron_variant		ENST00000332839.9	NP_066920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9	c.1808+33863A>T		intron_variant		1	NM_021097.5	ENSP00000332931	P4

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110504 AN: 151846 Hom.: 41651 Cov.: 31

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.728 AC: 110621 AN: 151964 Hom.: 41710 Cov.: 31 AF XY: 0.723 AC XY: 53679 AN XY: 74276

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.733

Alfa AF: 0.587 Hom.: 1806

Bravo AF: 0.745

Asia WGS AF: 0.518 AC: 1804 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.57
DANN	Benign	0.78

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: rs2192773; hg19: chr2-40621750;