rs13017846

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 ENST00000688930.2(ENSG00000287255):​n.317-2538A>G 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: ENSG00000287255 ENST00000688930.2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000688930.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A1	ENST00000405269.5	TSL:5	c.-25+80279T>C		intron	N/A	ENSP00000385535.1
	ENSG00000287255	ENST00000688930.2		n.317-2538A>G		intron	N/A
	ENSG00000287255	ENST00000703001.2		n.167-2538A>G		intron	N/A

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 v4.9

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;