rs17500300

Variant names:

• chr2-40121597-A-C
• rs17500300
• NM_021097.5:c.2546-5968T>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.2546-5968T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 152,174 control chromosomes in the GnomAD database, including 443 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 0.065 (443 hom., cov: 32)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• 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]

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0929 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.2546-5968T>G		intron	N/A	NP_066920.1
	SLC8A1	NM_001372263.2		c.2546-5968T>G		intron	N/A	NP_001359192.1
	SLC8A1	NM_001394103.1		c.2546-5968T>G		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.2546-5968T>G		intron	N/A	ENSP00000332931.4
	SLC8A1	ENST00000403092.5	TSL:1	c.2546-5968T>G		intron	N/A	ENSP00000384763.1
	SLC8A1	ENST00000405901.7	TSL:1	c.2531-5968T>G		intron	N/A	ENSP00000385678.3

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9921 AN: 152056 Hom.: 443 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0948

Gnomad OTH AF: 0.0555

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

GnomAD4 genome AF: 0.0652 AC: 9920 AN: 152174 Hom.: 443 Cov.: 32 AF XY: 0.0662 AC XY: 4925 AN XY: 74396

African (AFR) AF: 0.0175 AC: 728 AN: 41512

American (AMR) AF: 0.0492 AC: 752 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 130 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00996 AC: 48 AN: 4818

European-Finnish (FIN) AF: 0.144 AC: 1522 AN: 10574

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0948 AC: 6446 AN: 68000

Other (OTH) AF: 0.0549 AC: 116 AN: 2112

Alfa AF: 0.0797 Hom.: 294

Bravo AF: 0.0568

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.51
PhyloP100		-0.31
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: rs17500300; hg19: chr2-40348737;