rs394112

Variant names:

• chr2-40246710-C-A
• rs394112
• NM_021097.5:c.1809-68217G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-40246710-C-A
• chr2-40246710-C-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.1809-68217G>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
• Publications: 9 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]

SLC8A1-AS1 (HGNC:44102): (SLC8A1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1809-68217G>T		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.1809-68217G>T		intron_variant	Intron 2 of 10	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

African (AFR) AF: 0.218 AC: 9037 AN: 41520

American (AMR) AF: 0.202 AC: 3083 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 491 AN: 3466

East Asian (EAS) AF: 0.148 AC: 766 AN: 5178

South Asian (SAS) AF: 0.0642 AC: 310 AN: 4828

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10586

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.0866 AC: 5889 AN: 68002

Other (OTH) AF: 0.134 AC: 284 AN: 2112

Alfa AF: 0.133 Hom.: 291

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
PhyloP100		-0.045
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: rs394112; hg19: chr2-40473850;