chr2-40533825-T-C

Variant names:

• chr2-40533825-T-C
• rs17026156
• ENST00000405269.5:c.-25+77105A>G

Variant summary

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

The ENST00000405269.5(SLC8A1):​c.-25+77105A>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 152,272 control chromosomes in the GnomAD database, including 942 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 (942 hom., cov: 32)
• Consequence: SLC8A1 ENST00000405269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101929667	XR_007086295.1	n.236+567T>C		intron_variant	Intron 2 of 4
LOC101929667	XR_244991.5	n.315+567T>C		intron_variant	Intron 3 of 5
LOC101929667	XR_427021.5	n.236+567T>C		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000405269.5	c.-25+77105A>G		intron_variant	Intron 1 of 7	5		ENSP00000385535.1
ENSG00000287255	ENST00000688930.2	n.386+567T>C		intron_variant	Intron 4 of 6
ENSG00000287255	ENST00000703001.2	n.236+567T>C		intron_variant	Intron 2 of 4
ENSG00000287255	ENST00000703033.1	n.316+567T>C		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11149 AN: 152154 Hom.: 940 Cov.: 32

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0733 AC: 11160 AN: 152272 Hom.: 942 Cov.: 32 AF XY: 0.0771 AC XY: 5741 AN XY: 74452

African (AFR) AF: 0.0564 AC: 2345 AN: 41568

American (AMR) AF: 0.147 AC: 2245 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.428 AC: 2216 AN: 5174

South Asian (SAS) AF: 0.113 AC: 546 AN: 4824

European-Finnish (FIN) AF: 0.0524 AC: 556 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0434 AC: 2950 AN: 68022

Other (OTH) AF: 0.0852 AC: 180 AN: 2112

Alfa AF: 0.0610 Hom.: 885

Bravo AF: 0.0841

Asia WGS AF: 0.278 AC: 966 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.56
PhyloP100		-2.3
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: rs17026156; hg19: chr2-40760965;