chr2-40257934-C-T

Variant names:

• chr2-40257934-C-T
• rs434082
• NM_021097.5:c.1809-79441G>A

Variant summary

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

The NM_021097.5(SLC8A1):​c.1809-79441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,164 control chromosomes in the GnomAD database, including 1,605 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 0.14 (1605 hom., cov: 33)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 14 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021097.5. 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.1809-79441G>A		intron	N/A	NP_066920.1
	SLC8A1	NM_001372263.2		c.1809-79441G>A		intron	N/A	NP_001359192.1
	SLC8A1	NM_001394103.1		c.1809-79441G>A		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.1809-79441G>A		intron	N/A	ENSP00000332931.4
	SLC8A1	ENST00000403092.5	TSL:1	c.1809-79441G>A		intron	N/A	ENSP00000384763.1
	SLC8A1	ENST00000405901.7	TSL:1	c.1809-79441G>A		intron	N/A	ENSP00000385678.3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20729 AN: 152046 Hom.: 1601 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0672

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.136 AC: 20745 AN: 152164 Hom.: 1605 Cov.: 33 AF XY: 0.138 AC XY: 10296 AN XY: 74412

African (AFR) AF: 0.190 AC: 7888 AN: 41506

American (AMR) AF: 0.196 AC: 2995 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3472

East Asian (EAS) AF: 0.148 AC: 766 AN: 5172

South Asian (SAS) AF: 0.0670 AC: 323 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1377 AN: 10580

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.0963 AC: 6552 AN: 68008

Other (OTH) AF: 0.137 AC: 289 AN: 2108

Alfa AF: 0.113 Hom.: 1962

Bravo AF: 0.149

Asia WGS AF: 0.119 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.93
DANN	Benign	0.83
PhyloP100		-0.75
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: rs434082; hg19: chr2-40485074;