rs55788387

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001308093.3(GATA4):c.702G>A(p.Thr234=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,614,200 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 18 hom. )

Consequence

GATA4
NM_001308093.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.39

Variant links:

Genes affected

GATA4 (HGNC:4173): (GATA binding protein 4) This gene encodes a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function, and is necessary for normal testicular development. Mutations in this gene have been associated with cardiac septal defects. Additionally, alterations in gene expression have been associated with several cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

GATA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 8-11749001-G-A is Benign according to our data. Variant chr8-11749001-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 44335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11749001-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00358 (545/152322) while in subpopulation NFE AF= 0.0042 (286/68022). AF 95% confidence interval is 0.0038. There are 4 homozygotes in gnomad4. There are 299 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 545 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3 linkuse as main transcript	c.702G>A	p.Thr234=	synonymous_variant	3/7	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6 linkuse as main transcript	c.702G>A	p.Thr234=	synonymous_variant	3/7	1	NM_001308093.3	ENSP00000435712	A1	P43694-2

Frequencies

GnomAD3 genomes

AF:

0.00358

AC:

545

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00420

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00348

AC:

876

AN:

251486

Hom.:

AF XY:

0.00347

AC XY:

471

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000809

Gnomad ASJ exome

AF:

0.00575

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.0159

Gnomad NFE exome

AF:

0.00339

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00273

AC:

3986

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

2051

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00543

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.0150

Gnomad4 NFE exome

AF:

0.00244

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00358

AC:

545

AN:

152322

Hom.:

Cov.:

AF XY:

0.00401

AC XY:

299

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0175

Gnomad4 NFE

AF:

0.00420

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00377

Hom.:

Bravo

AF:

0.00214

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00376

EpiControl

AF:

0.00290

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	GATA4: BP4, BP7, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2011	Thr233Thr in exon 3 of GATA4: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located near a splice junction. It has been identified in 6 individuals with congenital hear t defects and in 1 of 518 control chromosomes (Schluterman 2007, Reamon-Buettner 2007, Tomita-Mitchell 2007, Butler 2010). It has also been reported in dbSNP wi th a similar allele frequency (rs55788387, MAF=0.002). -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 09, 2018	- -

Atrioventricular septal defect 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.033

DANN

Benign

0.68

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