2-40533825-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 ENST00000688930.2(ENSG00000287255):​n.386+567T>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 152,272 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: ENSG00000287255 ENST00000688930.2 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.

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+77105A>G		intron	N/A	ENSP00000385535.1	P32418-2
	ENSG00000287255	ENST00000688930.2		n.386+567T>C		intron	N/A
	ENSG00000287255	ENST00000703001.2		n.236+567T>C		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17026156;

hg19: chr2-40760965;