rs804280

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001308093.3(GATA4):c.1000+56C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,409,926 control chromosomes in the GnomAD database, including 277,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30361 hom., cov: 32)

Exomes 𝑓: 0.62 ( 247456 hom. )

Consequence

GATA4
NM_001308093.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1U:1B:10

Conservation

PhyloP100: -0.173

Publications

52 publications found

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 Gene-Disease associations (from GenCC):

atrial septal defect 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
structural congenital heart disease, multiple types - GATA4
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
testicular anomalies with or without congenital heart disease
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
metabolic syndrome
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
neonatal diabetes mellitus
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
pancreatic hypoplasia-diabetes-congenital heart disease syndrome
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
permanent neonatal diabetes mellitus
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
transient neonatal diabetes mellitus
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
46,XY partial gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tetralogy of fallot
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

GATA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-11755189-C-A is Benign according to our data. Variant chr8-11755189-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3 link	c.1000+56C>A		intron_variant	Intron 5 of 6	ENST00000532059.6	NP_001295022.1	P43694-2B3KUF4B6DU75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6 link	c.1000+56C>A		intron_variant	Intron 5 of 6	1	NM_001308093.3	ENSP00000435712.1		P43694-2

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94843

AN:

151966

Hom.:

30339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.588

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.981

Gnomad SAS

AF:

0.825

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.581

Gnomad OTH

AF:

0.611

GnomAD4 exome

AF:

0.618

AC:

777664

AN:

1257842

Hom.:

247456

AF XY:

0.622

AC XY:

394900

AN XY:

634466

show subpopulations

African (AFR)

AF:

0.581

AC:

17117

AN:

29448

American (AMR)

AF:

0.789

AC:

33704

AN:

42710

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

10797

AN:

24708

East Asian (EAS)

AF:

0.975

AC:

37644

AN:

38596

South Asian (SAS)

AF:

0.805

AC:

65206

AN:

80990

European-Finnish (FIN)

AF:

0.695

AC:

34745

AN:

49980

Middle Eastern (MID)

AF:

0.570

AC:

3056

AN:

5360

European-Non Finnish (NFE)

AF:

0.582

AC:

542611

AN:

932594

Other (OTH)

AF:

0.613

AC:

32784

AN:

53456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

14829

29658

44488

59317

74146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14064

28128

42192

56256

70320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.624

AC:

94911

AN:

152084

Hom.:

30361

Cov.:

AF XY:

0.638

AC XY:

47412

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.587

AC:

24366

AN:

41484

American (AMR)

AF:

0.713

AC:

10901

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1485

AN:

3470

East Asian (EAS)

AF:

0.980

AC:

5071

AN:

5172

South Asian (SAS)

AF:

0.823

AC:

3974

AN:

4826

European-Finnish (FIN)

AF:

0.718

AC:

7585

AN:

10564

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.581

AC:

39478

AN:

67956

Other (OTH)

AF:

0.615

AC:

1299

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1824

3647

5471

7294

9118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.601

Hom.:

90933

Bravo

AF:

0.623

Asia WGS

AF:

0.888

AC:

3086

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Uncertain:1Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2022

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Uncertain:1Benign:2

Molecular Genetics and Enzymology, National Research Centre

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25928801) -

Congenital heart disease

Pathogenic:1

Jan 07, 2017

Central Research Laboratory, Sri Devaraj Urs Academy of Higher Education and Research

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Atrioventricular septal defect 4

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GATA4-related disorder

Benign:1

Feb 16, 2021

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.56

(source)

DANN

Benign

0.55

PhyloP100

-0.17

Mutation Taster

=100/0

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over