rs394112

Positions:

• chr2-40246710-C-A
• chr2-40246710-C-G

Variant summary

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

The NM_021097.5(SLC8A1):​c.1809-68217G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,174 control chromosomes in the GnomAD database, including 1,802 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 0.14 (1802 hom., cov: 33)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1809-68217G>T		intron_variant		ENST00000332839.9	NP_066920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9	c.1809-68217G>T		intron_variant		1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21165 AN: 152056 Hom.: 1803 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.139 AC: 21172 AN: 152174 Hom.: 1802 Cov.: 33 AF XY: 0.140 AC XY: 10407 AN XY: 74406

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.0642

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0866

Gnomad4 OTH AF: 0.134

Alfa AF: 0.130 Hom.: 273

Bravo AF: 0.155

Asia WGS AF: 0.122 AC: 421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.80

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: rs394112; hg19: chr2-40473850;