chr2-40390680-C-T

Variant names:

• chr2-40390680-C-T
• rs2373859
• NM_021097.5:c.1808+37793G>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.1808+37793G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,016 control chromosomes in the GnomAD database, including 40,730 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 0.72 (40730 hom., cov: 32)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• 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]

LOC124905995 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021097.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A1	NM_021097.5	MANE Select	c.1808+37793G>A		intron	N/A	NP_066920.1	P32418-1
	SLC8A1	NM_001372263.2		c.1808+37793G>A		intron	N/A	NP_001359192.1	P32418-1
	SLC8A1	NM_001394103.1		c.1808+37793G>A		intron	N/A	NP_001381032.1	P32418-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A1	ENST00000332839.9	TSL:1 MANE Select	c.1808+37793G>A		intron	N/A	ENSP00000332931.4	P32418-1
	SLC8A1	ENST00000403092.5	TSL:1	c.1808+37793G>A		intron	N/A	ENSP00000384763.1	P32418-1
	SLC8A1	ENST00000405901.7	TSL:1	c.1808+37793G>A		intron	N/A	ENSP00000385678.3	P32418-5

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109010 AN: 151896 Hom.: 40674 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.718 AC: 109124 AN: 152016 Hom.: 40730 Cov.: 32 AF XY: 0.712 AC XY: 52872 AN XY: 74288

African (AFR) AF: 0.927 AC: 38507 AN: 41540

American (AMR) AF: 0.725 AC: 11040 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2438 AN: 3468

East Asian (EAS) AF: 0.363 AC: 1866 AN: 5142

South Asian (SAS) AF: 0.518 AC: 2500 AN: 4826

European-Finnish (FIN) AF: 0.636 AC: 6722 AN: 10568

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43767 AN: 67936

Other (OTH) AF: 0.718 AC: 1516 AN: 2112

Alfa AF: 0.666 Hom.: 58114

Bravo AF: 0.737

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.42
PhyloP100		-0.14
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: rs2373859; hg19: chr2-40617820;