2-40520865-T-G

Variant names:

• chr2-40520865-T-G
• rs4952632
• ENST00000405269.5:c.-25+90065A>C

Variant summary

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

The ENST00000688930.2(ENSG00000287255):​n.316+6475T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 152,030 control chromosomes in the GnomAD database, including 1,143 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 0.090 (1143 hom., cov: 32)
• Consequence: ENSG00000287255 ENST00000688930.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A1	ENST00000405269.5	TSL:5	c.-25+90065A>C		intron	N/A	ENSP00000385535.1
	ENSG00000287255	ENST00000688930.2		n.316+6475T>G		intron	N/A
	ENSG00000287255	ENST00000703001.2		n.166+8778T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0895 AC: 13591 AN: 151912 Hom.: 1140 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.0896 AC: 13618 AN: 152030 Hom.: 1143 Cov.: 32 AF XY: 0.0931 AC XY: 6925 AN XY: 74350

African (AFR) AF: 0.112 AC: 4650 AN: 41490

American (AMR) AF: 0.156 AC: 2375 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3466

East Asian (EAS) AF: 0.426 AC: 2187 AN: 5132

South Asian (SAS) AF: 0.113 AC: 547 AN: 4830

European-Finnish (FIN) AF: 0.0524 AC: 557 AN: 10620

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0438 AC: 2974 AN: 67940

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.0664 Hom.: 1832

Bravo AF: 0.104

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.48
PhyloP100		-0.46
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: rs4952632; hg19: chr2-40748005;