2-40578814-C-T

Position:

• chr2-40578814-C-T

Variant summary

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

The ENST00000405269.5(SLC8A1):​c.-25+32116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 151,910 control chromosomes in the GnomAD database, including 682 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 0.080 (682 hom., cov: 32)
• Consequence: SLC8A1 ENST00000405269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.40578814C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000405269.5	c.-25+32116G>A		intron_variant		5		ENSP00000385535.1

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12166 AN: 151792 Hom.: 681 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0656

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

GnomAD4 genome AF: 0.0801 AC: 12161 AN: 151910 Hom.: 682 Cov.: 32 AF XY: 0.0785 AC XY: 5828 AN XY: 74234

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0509

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.000583

Gnomad4 SAS AF: 0.0447

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0889 Hom.: 128

Bravo AF: 0.0709

Asia WGS AF: 0.0230 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.90
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10490258; hg19: chr2-40805954;