2-40291988-C-A

Variant names:

• chr2-40291988-C-A
• rs10490053
• NM_021097.5:c.1809-113495G>T

Variant summary

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

The NM_021097.5(SLC8A1):​c.1809-113495G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,066 control chromosomes in the GnomAD database, including 2,759 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 0.17 (2759 hom., cov: 31)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A1	NM_021097.5	MANE Select	c.1809-113495G>T		intron	N/A	NP_066920.1
	SLC8A1	NM_001372263.2		c.1809-113495G>T		intron	N/A	NP_001359192.1
	SLC8A1	NM_001394103.1		c.1809-113495G>T		intron	N/A	NP_001381032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A1	ENST00000332839.9	TSL:1 MANE Select	c.1809-113495G>T		intron	N/A	ENSP00000332931.4
	SLC8A1	ENST00000403092.5	TSL:1	c.1809-113495G>T		intron	N/A	ENSP00000384763.1
	SLC8A1	ENST00000405901.7	TSL:1	c.1809-113495G>T		intron	N/A	ENSP00000385678.3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26039 AN: 150958 Hom.: 2758 Cov.: 31

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.172 AC: 26046 AN: 151066 Hom.: 2759 Cov.: 31 AF XY: 0.179 AC XY: 13195 AN XY: 73698

African (AFR) AF: 0.0613 AC: 2522 AN: 41126

American (AMR) AF: 0.197 AC: 2986 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 757 AN: 3464

East Asian (EAS) AF: 0.369 AC: 1881 AN: 5102

South Asian (SAS) AF: 0.305 AC: 1459 AN: 4784

European-Finnish (FIN) AF: 0.248 AC: 2560 AN: 10326

Middle Eastern (MID) AF: 0.231 AC: 67 AN: 290

European-Non Finnish (NFE) AF: 0.195 AC: 13214 AN: 67846

Other (OTH) AF: 0.196 AC: 411 AN: 2092

Alfa AF: 0.172 Hom.: 2081

Bravo AF: 0.161

Asia WGS AF: 0.307 AC: 1065 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		0.30
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: rs10490053; hg19: chr2-40519128;