2-40265073-A-G

Position:

• chr2-40265073-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021097.5(SLC8A1):​c.1809-86580T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,204 control chromosomes in the GnomAD database, including 57,598 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 0.87 (57598 hom., cov: 32)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1809-86580T>C		intron_variant		ENST00000332839.9	NP_066920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9	c.1809-86580T>C		intron_variant		1	NM_021097.5	ENSP00000332931	P4

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131940 AN: 152086 Hom.: 57555 Cov.: 32

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.868 AC: 132042 AN: 152204 Hom.: 57598 Cov.: 32 AF XY: 0.862 AC XY: 64137 AN XY: 74396

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.855

Alfa AF: 0.855 Hom.: 9507

Bravo AF: 0.858

Asia WGS AF: 0.856 AC: 2978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.6
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs410259; hg19: chr2-40492213;