8-11756716-G-T

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.1001-219G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 612,510 control chromosomes in the GnomAD database, including 18,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3912 hom., cov: 33)

Exomes 𝑓: 0.21 ( 14926 hom. )

Consequence

GATA4
NM_001308093.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0230

Publications

14 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=-0.91).

BP6

Variant 8-11756716-G-T is Benign according to our data. Variant chr8-11756716-G-T is described in ClinVar as Benign. ClinVar VariationId is 1169507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 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
GATA4	NM_001308093.3	MANE Select	c.1001-219G>T	intron	N/A	NP_001295022.1
GATA4	NM_002052.5		c.998-219G>T	intron	N/A	NP_002043.2
GATA4	NM_001308094.2		c.380-219G>T	intron	N/A	NP_001295023.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GATA4	ENST00000532059.6	TSL:1 MANE Select	c.1001-219G>T	intron	N/A	ENSP00000435712.1
GATA4	ENST00000886854.1		c.1019-219G>T	intron	N/A	ENSP00000556913.1
GATA4	ENST00000886846.1		c.1001-219G>T	intron	N/A	ENSP00000556905.1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29906

AN:

151576

Hom.:

3905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.0341

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.682

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.195

GnomAD4 exome

AF:

0.211

AC:

97445

AN:

460816

Hom.:

14926

Cov.:

AF XY:

0.215

AC XY:

52194

AN XY:

242926

show subpopulations

African (AFR)

AF:

0.195

AC:

2485

AN:

12736

American (AMR)

AF:

0.310

AC:

5946

AN:

19180

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

1616

AN:

13978

East Asian (EAS)

AF:

0.659

AC:

20393

AN:

30948

South Asian (SAS)

AF:

0.319

AC:

15010

AN:

47084

European-Finnish (FIN)

AF:

0.234

AC:

7188

AN:

30700

Middle Eastern (MID)

AF:

0.230

AC:

459

AN:

1996

European-Non Finnish (NFE)

AF:

0.140

AC:

38947

AN:

277894

Other (OTH)

AF:

0.205

AC:

5401

AN:

26300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

3338

6676

10013

13351

16689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.197

AC:

29942

AN:

151694

Hom.:

3912

Cov.:

AF XY:

0.209

AC XY:

15514

AN XY:

74096

show subpopulations

African (AFR)

AF:

0.190

AC:

7880

AN:

41398

American (AMR)

AF:

0.266

AC:

4034

AN:

15162

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

427

AN:

3472

East Asian (EAS)

AF:

0.683

AC:

3520

AN:

5156

South Asian (SAS)

AF:

0.333

AC:

1596

AN:

4790

European-Finnish (FIN)

AF:

0.250

AC:

2624

AN:

10494

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9329

AN:

67926

Other (OTH)

AF:

0.197

AC:

412

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1125

2251

3376

4502

5627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.167

Hom.:

4408

Bravo

AF:

0.198

Asia WGS

AF:

0.482

AC:

1670

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Atrioventricular septal defect 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.6

(source)

DANN

Benign

0.63

PhyloP100

0.023

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over