rs10195113

Variant names:

• chr2-40605492-G-A
• rs10195113
• ENST00000405269.5:c.-25+5438C>T

Variant summary

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

The ENST00000405269.5(SLC8A1):​c.-25+5438C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 151,980 control chromosomes in the GnomAD database, including 224 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 0.045 (224 hom., cov: 32)
• Consequence: SLC8A1 ENST00000405269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

ENSG00000285898 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000405269.5	c.-25+5438C>T		intron_variant	Intron 1 of 7	5		ENSP00000385535.1
ENSG00000285898	ENST00000649978.1	n.448+10852G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6819 AN: 151862 Hom.: 224 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0446

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

GnomAD4 genome AF: 0.0448 AC: 6815 AN: 151980 Hom.: 224 Cov.: 32 AF XY: 0.0430 AC XY: 3197 AN XY: 74284

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0619

Gnomad4 FIN AF: 0.0250

Gnomad4 NFE AF: 0.0653

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0656 Hom.: 464

Bravo AF: 0.0441

Asia WGS AF: 0.0250 AC: 86 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10195113; hg19: chr2-40832632;