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/Likely benign criteria provided, multiple submitters, no conflicts P:1U:1B:11

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308093.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA4	NM_001308093.3	MANE Select	c.1000+56C>A	intron	N/A	NP_001295022.1	P43694-2
GATA4	NM_002052.5		c.997+56C>A	intron	N/A	NP_002043.2
GATA4	NM_001308094.2		c.379+56C>A	intron	N/A	NP_001295023.1	B3KUF4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA4	ENST00000532059.6	TSL:1 MANE Select	c.1000+56C>A	intron	N/A	ENSP00000435712.1	P43694-2
GATA4	ENST00000886854.1		c.1018+56C>A	intron	N/A	ENSP00000556913.1
GATA4	ENST00000886846.1		c.1000+56C>A	intron	N/A	ENSP00000556905.1

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (3)

Congenital heart disease (2)

Atrioventricular septal defect 4 (1)

GATA4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over