rs4952414

Variant names:

• chr2-40434165-G-A
• rs4952414
• NM_021097.5:c.-24-3861C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-40434165-G-A
• chr2-40434165-G-C
• chr2-40434165-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.-24-3861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,068 control chromosomes in the GnomAD database, including 36,576 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 0.68 (36576 hom., cov: 32)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.-24-3861C>T		intron_variant	Intron 1 of 10	ENST00000332839.9	NP_066920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9	c.-24-3861C>T		intron_variant	Intron 1 of 10	1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102601 AN: 151948 Hom.: 36507 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.676 AC: 102735 AN: 152068 Hom.: 36576 Cov.: 32 AF XY: 0.683 AC XY: 50787 AN XY: 74326

African (AFR) AF: 0.865 AC: 35926 AN: 41512

American (AMR) AF: 0.717 AC: 10948 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2191 AN: 3470

East Asian (EAS) AF: 0.932 AC: 4807 AN: 5158

South Asian (SAS) AF: 0.835 AC: 4031 AN: 4826

European-Finnish (FIN) AF: 0.637 AC: 6724 AN: 10562

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35967 AN: 67962

Other (OTH) AF: 0.645 AC: 1363 AN: 2114

Alfa AF: 0.584 Hom.: 33385

Bravo AF: 0.690

Asia WGS AF: 0.875 AC: 3041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.64
PhyloP100		1.1
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: rs4952414; hg19: chr2-40661305;