Variant 2-40115460-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_021097.5(SLC8A1):c.2715C>A(p.Gly905=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00918 in 1,614,176 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 82 hom. )

Consequence

SLC8A1
NM_021097.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.84

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 2-40115460-G-T is Benign according to our data. Variant chr2-40115460-G-T is described in ClinVar as [Benign]. Clinvar id is 781601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC8A1	NM_021097.5 linkuse as main transcript	c.2715C>A	p.Gly905=	synonymous_variant	11/11	ENST00000332839.9
SLC8A1-AS1	NR_038441.1 linkuse as main transcript	n.121+10498G>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.2715C>A	p.Gly905=	synonymous_variant	11/11	1	NM_021097.5	P4	P32418-1
SLC8A1-AS1	ENST00000599740.1 linkuse as main transcript	n.74-136224G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

1115

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00758

AC:

1907

AN:

251420

Hom.:

AF XY:

0.00771

AC XY:

1048

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00854

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00444

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00864

GnomAD4 exome

AF:

0.00938

AC:

13709

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00917

AC XY:

6669

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.00792

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00466

Gnomad4 FIN exome

AF:

0.0149

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.00773

GnomAD4 genome

AF:

0.00731

AC:

1113

AN:

152302

Hom.:

Cov.:

AF XY:

0.00726

AC XY:

541

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.0108

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00915

Hom.:

Bravo

AF:

0.00617

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00976

EpiControl

AF:

0.00776

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.89

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