rs745379

Variant names:

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.1150-107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,092,154 control chromosomes in the GnomAD database, including 114,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12854 hom., cov: 32)

Exomes 𝑓: 0.45 ( 101174 hom. )

Consequence

GATA4
NM_001308093.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:7

Conservation

PhyloP100: 0.0220

Publications

13 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=-0.94).

BP6

Variant 8-11758186-A-G is Benign according to our data. Variant chr8-11758186-A-G is described in ClinVar as Benign. ClinVar VariationId is 433015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3 link	c.1150-107A>G		intron_variant	Intron 6 of 6	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6 link	c.1150-107A>G		intron_variant	Intron 6 of 6	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58856

AN:

151944

Hom.:

12850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.0220

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.446

AC:

419686

AN:

940092

Hom.:

101174

AF XY:

0.447

AC XY:

218518

AN XY:

489278

show subpopulations

African (AFR)

AF:

0.258

AC:

6046

AN:

23478

American (AMR)

AF:

0.236

AC:

10223

AN:

43396

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

14244

AN:

22854

East Asian (EAS)

AF:

0.0260

AC:

972

AN:

37330

South Asian (SAS)

AF:

0.336

AC:

25357

AN:

75424

European-Finnish (FIN)

AF:

0.369

AC:

16663

AN:

45218

Middle Eastern (MID)

AF:

0.496

AC:

1643

AN:

3312

European-Non Finnish (NFE)

AF:

0.504

AC:

325296

AN:

645774

Other (OTH)

AF:

0.444

AC:

19242

AN:

43306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

12233

24466

36700

48933

61166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6632

13264

19896

26528

33160

<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:

0.387

AC:

58889

AN:

152062

Hom.:

12854

Cov.:

AF XY:

0.373

AC XY:

27734

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.258

AC:

10683

AN:

41474

American (AMR)

AF:

0.313

AC:

4785

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.639

AC:

2214

AN:

3466

East Asian (EAS)

AF:

0.0219

AC:

113

AN:

5170

South Asian (SAS)

AF:

0.314

AC:

1515

AN:

4818

European-Finnish (FIN)

AF:

0.347

AC:

3675

AN:

10594

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.508

AC:

34481

AN:

67932

Other (OTH)

AF:

0.418

AC:

883

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1773

3545

5318

7090

8863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.434

Hom.:

1809

Bravo

AF:

0.377

Asia WGS

AF:

0.148

AC:

517

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 28, 2020

H3Africa Consortium

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.229, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Congenital heart disease

Pathogenic:1Benign: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

- -

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:curation

NG_008177.2(NM_002052.4):c.1147-107A>G in the gene GATA4 has an allele frequency of 0.510 in European (non-Finnish) subpopulation in the gnomAD database. 2668 homozygous occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1; BS2. -

not provided

Benign:1

Mar 31, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

3.7

(source)

DANN

Benign

0.38

PhyloP100

0.022

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

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over