2-40226654-A-G

Position:

• chr2-40226654-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.1809-48161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,000 control chromosomes in the GnomAD database, including 15,907 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 0.42 (15907 hom., cov: 32)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1809-48161T>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.1809-48161T>C		intron_variant		1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63895 AN: 151880 Hom.: 15902 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.420 AC: 63914 AN: 152000 Hom.: 15907 Cov.: 32 AF XY: 0.414 AC XY: 30769 AN XY: 74286

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.462

Alfa AF: 0.550 Hom.: 32255

Bravo AF: 0.408

Asia WGS AF: 0.331 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.74

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: rs10490208; hg19: chr2-40453794;