chr2-40156500-AAAAG-A

Variant names:

• chr2-40156500-AAAAG-A
• rs10611760
• NM_021097.5:c.2269+4261_2269+4264delCTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000332839.9(SLC8A1):​c.2269+4261_2269+4264delCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.96 (69756 hom., cov: 0)
• Consequence: SLC8A1 ENST00000332839.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 0 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]

SLC8A1-AS1 (HGNC:44102): (SLC8A1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000332839.9. 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
	SLC8A1	NM_021097.5	MANE Select	c.2269+4261_2269+4264delCTTT		intron	N/A	NP_066920.1
	SLC8A1	NM_001372263.2		c.2269+4261_2269+4264delCTTT		intron	N/A	NP_001359192.1
	SLC8A1	NM_001394103.1		c.2269+4261_2269+4264delCTTT		intron	N/A	NP_001381032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A1	ENST00000332839.9	TSL:1 MANE Select	c.2269+4261_2269+4264delCTTT		intron	N/A	ENSP00000332931.4
	SLC8A1	ENST00000403092.5	TSL:1	c.2269+4261_2269+4264delCTTT		intron	N/A	ENSP00000384763.1
	SLC8A1	ENST00000405901.7	TSL:1	c.2254+4261_2254+4264delCTTT		intron	N/A	ENSP00000385678.3

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145142 AN: 151650 Hom.: 69708 Cov.: 0

Gnomad AFR AF: 0.875

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.980

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.962

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

GnomAD4 genome AF: 0.957 AC: 145247 AN: 151770 Hom.: 69756 Cov.: 0 AF XY: 0.957 AC XY: 71008 AN XY: 74186

African (AFR) AF: 0.875 AC: 36122 AN: 41260

American (AMR) AF: 0.985 AC: 15033 AN: 15264

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3471 AN: 3472

East Asian (EAS) AF: 0.822 AC: 4198 AN: 5108

South Asian (SAS) AF: 0.980 AC: 4706 AN: 4804

European-Finnish (FIN) AF: 1.00 AC: 10574 AN: 10574

Middle Eastern (MID) AF: 0.990 AC: 289 AN: 292

European-Non Finnish (NFE) AF: 0.999 AC: 67923 AN: 67974

Other (OTH) AF: 0.957 AC: 2021 AN: 2112

Alfa AF: 0.975 Hom.: 7770

Bravo AF: 0.950

Asia WGS AF: 0.903 AC: 3138 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10611760; hg19: chr2-40383640;