chr2-40326550-G-C

Variant names:

• chr2-40326550-G-C
• rs72943138
• NM_021097.5:c.1808+101923C>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.1808+101923C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,890 control chromosomes in the GnomAD database, including 1,887 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 0.15 (1887 hom., cov: 32)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1808+101923C>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.1808+101923C>G		intron_variant	Intron 2 of 10	1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22284 AN: 151774 Hom.: 1881 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.0883

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.147 AC: 22299 AN: 151890 Hom.: 1887 Cov.: 32 AF XY: 0.147 AC XY: 10884 AN XY: 74210

African (AFR) AF: 0.215 AC: 8910 AN: 41416

American (AMR) AF: 0.182 AC: 2779 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1101 AN: 5156

South Asian (SAS) AF: 0.0877 AC: 422 AN: 4810

European-Finnish (FIN) AF: 0.111 AC: 1172 AN: 10516

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6952 AN: 67942

Other (OTH) AF: 0.152 AC: 320 AN: 2112

Alfa AF: 0.129 Hom.: 174

Bravo AF: 0.159

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.70
PhyloP100		0.12
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: rs72943138; hg19: chr2-40553690;