8-11748803-T-C

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.617-113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,276,656 control chromosomes in the GnomAD database, including 374,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49802 hom., cov: 33)

Exomes 𝑓: 0.76 ( 324915 hom. )

Consequence

GATA4
NM_001308093.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:10

Conservation

PhyloP100: 0.332

Publications

5 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=-0.87).

BP6

Variant 8-11748803-T-C is Benign according to our data. Variant chr8-11748803-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 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.617-113T>C	intron	N/A	NP_001295022.1	P43694-2
GATA4	NM_002052.5		c.617-116T>C	intron	N/A	NP_002043.2
GATA4	NM_001308094.2		c.-5-113T>C	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.617-113T>C	intron	N/A	ENSP00000435712.1	P43694-2
GATA4	ENST00000886854.1		c.617-116T>C	intron	N/A	ENSP00000556913.1
GATA4	ENST00000886846.1		c.617-113T>C	intron	N/A	ENSP00000556905.1

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

122250

AN:

152134

Hom.:

49742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.898

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.815

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.984

Gnomad SAS

AF:

0.888

Gnomad FIN

AF:

0.849

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.728

Gnomad OTH

AF:

0.764

GnomAD4 exome

AF:

0.756

AC:

849976

AN:

1124404

Hom.:

324915

AF XY:

0.759

AC XY:

436396

AN XY:

575192

show subpopulations

African (AFR)

AF:

0.905

AC:

24116

AN:

26660

American (AMR)

AF:

0.859

AC:

37938

AN:

44144

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

15425

AN:

23976

East Asian (EAS)

AF:

0.976

AC:

37233

AN:

38138

South Asian (SAS)

AF:

0.876

AC:

69109

AN:

78860

European-Finnish (FIN)

AF:

0.833

AC:

42549

AN:

51052

Middle Eastern (MID)

AF:

0.743

AC:

3516

AN:

4730

European-Non Finnish (NFE)

AF:

0.722

AC:

582875

AN:

807632

Other (OTH)

AF:

0.756

AC:

37215

AN:

49212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

10485

20970

31454

41939

52424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12534

25068

37602

50136

62670

<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:

0.804

AC:

122370

AN:

152252

Hom.:

49802

Cov.:

AF XY:

0.813

AC XY:

60534

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.898

AC:

37302

AN:

41542

American (AMR)

AF:

0.815

AC:

12478

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

2205

AN:

3470

East Asian (EAS)

AF:

0.984

AC:

5101

AN:

5186

South Asian (SAS)

AF:

0.887

AC:

4281

AN:

4826

European-Finnish (FIN)

AF:

0.849

AC:

9021

AN:

10620

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.728

AC:

49522

AN:

67986

Other (OTH)

AF:

0.766

AC:

1620

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1231

2461

3692

4922

6153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.764

Hom.:

68156

Bravo

AF:

0.804

Asia WGS

AF:

0.937

AC:

3258

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 (4)

Congenital heart disease (3)

not provided (3)

Structural congenital heart disease, multiple types - GATA4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.1

(source)

DANN

Benign

0.67

PhyloP100

0.33

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