Variant 2-40177826-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000406391.2(SLC8A1):c.1838G>A(p.Arg613His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,550,724 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 22 hom. )

Consequence

SLC8A1
ENST00000406391.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.828

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00810191).

BP6

Variant 2-40177826-C-T is Benign according to our data. Variant chr2-40177826-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650849.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-40177826-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 696 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC8A1	NM_021097.5 linkuse as main transcript	c.1915+561G>A		intron_variant		ENST00000332839.9
SLC8A1-AS1	NR_038441.1 linkuse as main transcript	n.121+72864C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC8A1	ENST00000332839.9 linkuse as main transcript	c.1915+561G>A		intron_variant		1	NM_021097.5	P4	P32418-1
SLC8A1-AS1	ENST00000599740.1 linkuse as main transcript	n.74-73858C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00457

AC:

695

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00348

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00628

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00375

AC:

587

AN:

156610

Hom.:

AF XY:

0.00370

AC XY:

307

AN XY:

82944

show subpopulations

Gnomad AFR exome

AF:

0.00239

Gnomad AMR exome

AF:

0.00227

Gnomad ASJ exome

AF:

0.00212

Gnomad EAS exome

AF:

0.0000903

Gnomad SAS exome

AF:

0.00224

Gnomad FIN exome

AF:

0.00362

Gnomad NFE exome

AF:

0.00574

Gnomad OTH exome

AF:

0.00776

GnomAD4 exome

AF:

0.00541

AC:

7559

AN:

1398494

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

3678

AN XY:

689806

show subpopulations

Gnomad4 AFR exome

AF:

0.00339

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.00278

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00241

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.00616

Gnomad4 OTH exome

AF:

0.00462

GnomAD4 genome

AF:

0.00457

AC:

696

AN:

152230

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

299

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00347

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.00628

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00497

Hom.:

Bravo

AF:

0.00482

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00506

AC:

ESP6500EA

AF:

0.00660

AC:

ExAC

AF:

0.00347

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

SLC8A1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.90

.;.;.;D;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0081

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;N;N;N;N;N;N

PROVEAN

Benign

0.70

N;N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.052

T;T;T;T;T

Sift4G

Uncertain

0.034

D;D;D;D;D

Polyphen

0.31

B;B;B;P;B

Vest4

0.19

MVP

0.38

ClinPred

0.019

GERP RS

3.5

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over