chr2-40197304-G-A

Variant names:

• chr2-40197304-G-A
• rs449383
• NM_021097.5:c.1809-18811C>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.1809-18811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,794 control chromosomes in the GnomAD database, including 28,002 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 0.60 (28002 hom., cov: 32)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• Publications: 9 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]

SLC8A1-AS1 (HGNC:44102): (SLC8A1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 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.1809-18811C>T		intron	N/A	NP_066920.1
	SLC8A1	NM_001372263.2		c.1809-18811C>T		intron	N/A	NP_001359192.1
	SLC8A1	NM_001394103.1		c.1809-18811C>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.1809-18811C>T		intron	N/A	ENSP00000332931.4
	SLC8A1	ENST00000403092.5	TSL:1	c.1809-18811C>T		intron	N/A	ENSP00000384763.1
	SLC8A1	ENST00000405901.7	TSL:1	c.1809-18811C>T		intron	N/A	ENSP00000385678.3

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90454 AN: 151674 Hom.: 27995 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.596 AC: 90489 AN: 151794 Hom.: 28002 Cov.: 32 AF XY: 0.590 AC XY: 43779 AN XY: 74174

African (AFR) AF: 0.450 AC: 18626 AN: 41400

American (AMR) AF: 0.648 AC: 9866 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2447 AN: 3466

East Asian (EAS) AF: 0.381 AC: 1962 AN: 5144

South Asian (SAS) AF: 0.506 AC: 2436 AN: 4816

European-Finnish (FIN) AF: 0.610 AC: 6442 AN: 10558

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46437 AN: 67880

Other (OTH) AF: 0.631 AC: 1331 AN: 2108

Alfa AF: 0.668 Hom.: 45069

Bravo AF: 0.595

Asia WGS AF: 0.461 AC: 1603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.6
DANN	Benign	0.73
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: rs449383; hg19: chr2-40424444;