chr2-40530651-A-G

Variant names:

• chr2-40530651-A-G
• rs13017846
• ENST00000405269.5:c.-25+80279T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000405269.5(SLC8A1):​c.-25+80279T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 152,218 control chromosomes in the GnomAD database, including 940 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 0.073 (940 hom., cov: 32)
• Consequence: SLC8A1 ENST00000405269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 16 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]

ENSG00000287255 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101929667	XR_007086295.1	n.167-2538A>G		intron_variant	Intron 1 of 4
LOC101929667	XR_244991.5	n.246-2538A>G		intron_variant	Intron 2 of 5
LOC101929667	XR_427021.5	n.167-2538A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000405269.5	c.-25+80279T>C		intron_variant	Intron 1 of 7	5		ENSP00000385535.1
ENSG00000287255	ENST00000688930.2	n.317-2538A>G		intron_variant	Intron 3 of 6
ENSG00000287255	ENST00000703001.2	n.167-2538A>G		intron_variant	Intron 1 of 4
ENSG00000287255	ENST00000703033.1	n.247-2538A>G		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11142 AN: 152100 Hom.: 938 Cov.: 32

Gnomad AFR AF: 0.0568

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0733 AC: 11152 AN: 152218 Hom.: 940 Cov.: 32 AF XY: 0.0771 AC XY: 5737 AN XY: 74408

African (AFR) AF: 0.0568 AC: 2358 AN: 41546

American (AMR) AF: 0.147 AC: 2241 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2214 AN: 5162

South Asian (SAS) AF: 0.112 AC: 539 AN: 4822

European-Finnish (FIN) AF: 0.0522 AC: 554 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0432 AC: 2941 AN: 68008

Other (OTH) AF: 0.0876 AC: 185 AN: 2112

Alfa AF: 0.0592 Hom.: 1543

Bravo AF: 0.0840

Asia WGS AF: 0.277 AC: 962 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.44
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13017846; hg19: chr2-40757791;