2-40316088-C-T

Variant names:

• chr2-40316088-C-T
• rs998260
• NM_021097.5:c.1808+112385G>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+112385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,856 control chromosomes in the GnomAD database, including 21,571 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 0.50 (21571 hom., cov: 32)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1808+112385G>A		intron_variant	Intron 2 of 10	ENST00000332839.9	NP_066920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9	c.1808+112385G>A		intron_variant	Intron 2 of 10	1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75884 AN: 151738 Hom.: 21526 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.500 AC: 75987 AN: 151856 Hom.: 21571 Cov.: 32 AF XY: 0.504 AC XY: 37422 AN XY: 74206

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.480

Alfa AF: 0.391 Hom.: 5640

Bravo AF: 0.520

Asia WGS AF: 0.567 AC: 1969 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.70

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: rs998260; hg19: chr2-40543228;