2-40439867-C-T

Variant names:

• chr2-40439867-C-T
• rs1990609
• NM_021097.5:c.-24-9563G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021097.5(SLC8A1):​c.-24-9563G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,984 control chromosomes in the GnomAD database, including 21,219 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 (21219 hom., cov: 33)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.-24-9563G>A		intron_variant	Intron 1 of 10	ENST00000332839.9	NP_066920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9	c.-24-9563G>A		intron_variant	Intron 1 of 10	1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76601 AN: 151868 Hom.: 21161 Cov.: 33

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.505 AC: 76721 AN: 151984 Hom.: 21219 Cov.: 33 AF XY: 0.515 AC XY: 38252 AN XY: 74294

African (AFR) AF: 0.695 AC: 28811 AN: 41450

American (AMR) AF: 0.588 AC: 8961 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1591 AN: 3470

East Asian (EAS) AF: 0.687 AC: 3535 AN: 5148

South Asian (SAS) AF: 0.635 AC: 3069 AN: 4830

European-Finnish (FIN) AF: 0.513 AC: 5429 AN: 10582

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23797 AN: 67948

Other (OTH) AF: 0.499 AC: 1052 AN: 2110

Alfa AF: 0.390 Hom.: 8146

Bravo AF: 0.520

Asia WGS AF: 0.666 AC: 2308 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.55
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1990609; hg19: chr2-40667007;