rs17025867

Variant names:

• chr2-40351419-G-A
• rs17025867
• NM_021097.5:c.1808+77054C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-40351419-G-A
• chr2-40351419-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021097.5(SLC8A1):​c.1808+77054C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 151,744 control chromosomes in the GnomAD database, including 24 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 0.014 (24 hom., cov: 31)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 9 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=-0.89).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.014 (2120/151744) while in subpopulation SAS AF = 0.0451 (217/4816). AF 95% confidence interval is 0.0401. There are 24 homozygotes in GnomAd4. There are 984 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2120 AD gene.

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.1808+77054C>T		intron	N/A	NP_066920.1
	SLC8A1	NM_001372263.2		c.1808+77054C>T		intron	N/A	NP_001359192.1
	SLC8A1	NM_001394103.1		c.1808+77054C>T		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.1808+77054C>T		intron	N/A	ENSP00000332931.4
	SLC8A1	ENST00000403092.5	TSL:1	c.1808+77054C>T		intron	N/A	ENSP00000384763.1
	SLC8A1	ENST00000405901.7	TSL:1	c.1808+77054C>T		intron	N/A	ENSP00000385678.3

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2128 AN: 151628 Hom.: 24 Cov.: 31

Gnomad AFR AF: 0.00909

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00801

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.00548

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0139

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

GnomAD4 genome AF: 0.0140 AC: 2120 AN: 151744 Hom.: 24 Cov.: 31 AF XY: 0.0133 AC XY: 984 AN XY: 74188

African (AFR) AF: 0.00907 AC: 373 AN: 41144

American (AMR) AF: 0.00800 AC: 122 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.0451 AC: 217 AN: 4816

European-Finnish (FIN) AF: 0.00548 AC: 58 AN: 10592

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0181 AC: 1234 AN: 67996

Other (OTH) AF: 0.0137 AC: 29 AN: 2110

Alfa AF: 0.0112 Hom.: 8

Bravo AF: 0.0129

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.38
PhyloP100		-0.075
Mutation Taster		=100/0	polymorphism

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: rs17025867; hg19: chr2-40578559;