2-40257805-T-C

Variant names:

• chr2-40257805-T-C
• rs3749056
• NM_021097.5:c.1809-79312A>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.1809-79312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,202 control chromosomes in the GnomAD database, including 52,199 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 0.82 (52199 hom., cov: 34)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647
• Publications: 4 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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1809-79312A>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.1809-79312A>G		intron_variant	Intron 2 of 10	1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124843 AN: 152084 Hom.: 52159 Cov.: 34

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.821 AC: 124937 AN: 152202 Hom.: 52199 Cov.: 34 AF XY: 0.821 AC XY: 61099 AN XY: 74418

African (AFR) AF: 0.662 AC: 27448 AN: 41474

American (AMR) AF: 0.788 AC: 12056 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3003 AN: 3472

East Asian (EAS) AF: 0.851 AC: 4405 AN: 5176

South Asian (SAS) AF: 0.931 AC: 4491 AN: 4822

European-Finnish (FIN) AF: 0.869 AC: 9225 AN: 10612

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 61457 AN: 68028

Other (OTH) AF: 0.832 AC: 1759 AN: 2114

Alfa AF: 0.864 Hom.: 36431

Bravo AF: 0.802

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.9
DANN	Benign	0.85
PhyloP100		0.65
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: rs3749056; hg19: chr2-40484945;