Genetic Variant SLC8A1:c.1809-76565_1809-76564insTGGAGAGGGAATGA (chr2-40255057-T-TTCATTCCCTCTCCA) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_021097.5(SLC8A1):c.1809-76565_1809-76564insTGGAGAGGGAATGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,864 control chromosomes in the GnomAD database, including 1,790 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1790 hom., cov: 30)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

SLC8A1
NM_021097.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.300

Publications

1 publications found

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]

SLC8A1 links:

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

SLC8A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC8A1	NM_021097.5 link	c.1809-76565_1809-76564insTGGAGAGGGAATGA		intron_variant	Intron 2 of 10	ENST00000332839.9	NP_066920.1	P32418-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9 link	c.1809-76565_1809-76564insTGGAGAGGGAATGA		intron_variant	Intron 2 of 10	1	NM_021097.5	ENSP00000332931.4		P32418-1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20939

AN:

151740

Hom.:

1790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.0624

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.0854

Gnomad OTH

AF:

0.131

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.138

AC:

20948

AN:

151858

Hom.:

1790

Cov.:

AF XY:

0.139

AC XY:

10294

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.219

AC:

9097

AN:

41486

American (AMR)

AF:

0.198

AC:

3010

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

473

AN:

3450

East Asian (EAS)

AF:

0.136

AC:

701

AN:

5136

South Asian (SAS)

AF:

0.0621

AC:

294

AN:

4738

European-Finnish (FIN)

AF:

0.113

AC:

1203

AN:

10602

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0854

AC:

5800

AN:

67928

Other (OTH)

AF:

0.130

AC:

274

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

822

1644

2466

3288

4110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0426

Hom.:

Asia WGS

AF:

0.116

AC:

404

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over