chr2-40316088-C-T

Variant names:

• chr2-40316088-C-T
• rs998260
• NM_021097.5:c.1808+112385G>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+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
• Publications: 1 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 = 0.756 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+112385G>A		intron	N/A	NP_066920.1	P32418-1
	SLC8A1	NM_001372263.2		c.1808+112385G>A		intron	N/A	NP_001359192.1	P32418-1
	SLC8A1	NM_001394103.1		c.1808+112385G>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+112385G>A		intron	N/A	ENSP00000332931.4	P32418-1
	SLC8A1	ENST00000403092.5	TSL:1	c.1808+112385G>A		intron	N/A	ENSP00000384763.1	P32418-1
	SLC8A1	ENST00000405901.7	TSL:1	c.1808+112385G>A		intron	N/A	ENSP00000385678.3	P32418-5

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

African (AFR) AF: 0.763 AC: 31665 AN: 41478

American (AMR) AF: 0.489 AC: 7427 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1421 AN: 3468

East Asian (EAS) AF: 0.700 AC: 3602 AN: 5144

South Asian (SAS) AF: 0.446 AC: 2148 AN: 4818

European-Finnish (FIN) AF: 0.454 AC: 4794 AN: 10554

Middle Eastern (MID) AF: 0.497 AC: 144 AN: 290

European-Non Finnish (NFE) AF: 0.345 AC: 23435 AN: 67890

Other (OTH) AF: 0.480 AC: 1013 AN: 2110

Alfa AF: 0.388 Hom.: 6187

Bravo AF: 0.520

Asia WGS AF: 0.567 AC: 1969 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.70
PhyloP100		0.51
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: rs998260; hg19: chr2-40543228;