rs6544318

Variant names:

• chr2-40300525-G-A
• rs6544318
• NM_021097.5:c.1809-122032C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-40300525-G-A
• chr2-40300525-G-C
• chr2-40300525-G-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.1809-122032C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,018 control chromosomes in the GnomAD database, including 20,456 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 0.49 (20456 hom., cov: 32)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1809-122032C>T		intron_variant	Intron 2 of 10	ENST00000332839.9	NP_066920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9	c.1809-122032C>T		intron_variant	Intron 2 of 10	1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74651 AN: 151902 Hom.: 20420 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.492 AC: 74744 AN: 152018 Hom.: 20456 Cov.: 32 AF XY: 0.495 AC XY: 36799 AN XY: 74296

African (AFR) AF: 0.718 AC: 29783 AN: 41490

American (AMR) AF: 0.492 AC: 7506 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1451 AN: 3470

East Asian (EAS) AF: 0.720 AC: 3710 AN: 5156

South Asian (SAS) AF: 0.490 AC: 2356 AN: 4812

European-Finnish (FIN) AF: 0.436 AC: 4604 AN: 10558

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23830 AN: 67962

Other (OTH) AF: 0.478 AC: 1008 AN: 2108

Alfa AF: 0.372 Hom.: 6673

Bravo AF: 0.511

Asia WGS AF: 0.596 AC: 2070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.55
PhyloP100		0.16
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: rs6544318; hg19: chr2-40527665;