rs666362

Variant names:

• chr2-40232505-T-C
• rs666362
• NM_021097.5:c.1809-54012A>G

Variant summary

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

The NM_021097.5(SLC8A1):​c.1809-54012A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 151,358 control chromosomes in the GnomAD database, including 2,570 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 0.16 (2570 hom., cov: 28)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• 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]

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1809-54012A>G		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.1809-54012A>G		intron_variant	Intron 2 of 10	1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24132 AN: 151242 Hom.: 2565 Cov.: 28

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.160 AC: 24170 AN: 151358 Hom.: 2570 Cov.: 28 AF XY: 0.160 AC XY: 11788 AN XY: 73900

African (AFR) AF: 0.288 AC: 11865 AN: 41200

American (AMR) AF: 0.206 AC: 3120 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3468

East Asian (EAS) AF: 0.139 AC: 714 AN: 5142

South Asian (SAS) AF: 0.0646 AC: 309 AN: 4784

European-Finnish (FIN) AF: 0.116 AC: 1217 AN: 10464

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.0891 AC: 6042 AN: 67832

Other (OTH) AF: 0.145 AC: 304 AN: 2096

Alfa AF: 0.109 Hom.: 865

Bravo AF: 0.177

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.64
PhyloP100		-1.3
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: rs666362; hg19: chr2-40459645;