rs404005

Variant names:

• chr2-40168938-C-T
• rs404005
• NM_021097.5:c.2038+1343G>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.2038+1343G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,110 control chromosomes in the GnomAD database, including 27,260 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 0.59 (27260 hom., cov: 33)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• 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]

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

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 (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.2038+1343G>A		intron_variant	Intron 7 of 10	ENST00000332839.9	NP_066920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9	c.2038+1343G>A		intron_variant	Intron 7 of 10	1	NM_021097.5	ENSP00000332931.4

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89199 AN: 151992 Hom.: 27240 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.587 AC: 89258 AN: 152110 Hom.: 27260 Cov.: 33 AF XY: 0.582 AC XY: 43229 AN XY: 74338

African (AFR) AF: 0.432 AC: 17941 AN: 41490

American (AMR) AF: 0.650 AC: 9937 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2485 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1845 AN: 5170

South Asian (SAS) AF: 0.508 AC: 2450 AN: 4824

European-Finnish (FIN) AF: 0.597 AC: 6303 AN: 10556

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46030 AN: 67996

Other (OTH) AF: 0.624 AC: 1320 AN: 2116

Alfa AF: 0.648 Hom.: 61557

Bravo AF: 0.586

Asia WGS AF: 0.447 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.99
DANN	Benign	0.62
PhyloP100		-0.59
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: rs404005; hg19: chr2-40396078;