rs2110922

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021097.5(SLC8A1):​c.2545+2897G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,944 control chromosomes in the GnomAD database, including 12,634 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 0.40 ( 12634 hom., cov: 32)

Consequence

SLC8A1
NM_021097.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.895
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC8A1NM_021097.5 linkuse as main transcriptc.2545+2897G>T intron_variant ENST00000332839.9 NP_066920.1 P32418-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC8A1ENST00000332839.9 linkuse as main transcriptc.2545+2897G>T intron_variant 1 NM_021097.5 ENSP00000332931.4 P32418-1

Frequencies

GnomAD3 genomes
AF:
0.404
AC:
61412
AN:
151826
Hom.:
12619
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.447
Gnomad AMI
AF:
0.275
Gnomad AMR
AF:
0.357
Gnomad ASJ
AF:
0.342
Gnomad EAS
AF:
0.517
Gnomad SAS
AF:
0.469
Gnomad FIN
AF:
0.478
Gnomad MID
AF:
0.285
Gnomad NFE
AF:
0.371
Gnomad OTH
AF:
0.362
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.404
AC:
61453
AN:
151944
Hom.:
12634
Cov.:
32
AF XY:
0.412
AC XY:
30554
AN XY:
74250
show subpopulations
Gnomad4 AFR
AF:
0.447
Gnomad4 AMR
AF:
0.358
Gnomad4 ASJ
AF:
0.342
Gnomad4 EAS
AF:
0.517
Gnomad4 SAS
AF:
0.468
Gnomad4 FIN
AF:
0.478
Gnomad4 NFE
AF:
0.371
Gnomad4 OTH
AF:
0.364
Alfa
AF:
0.368
Hom.:
13399
Bravo
AF:
0.392
Asia WGS
AF:
0.481
AC:
1670
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.14
DANN
Benign
0.49

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2110922; hg19: chr2-40363644; API