GeneBe

8-11708843-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001308093.3(GATA4):​c.531C>T​(p.Ala177Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,346,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A177A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

GATA4
NM_001308093.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.32

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP7
Synonymous conserved (PhyloP=-2.32 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GATA4NM_001308093.3 linkc.531C>T p.Ala177Ala synonymous_variant Exon 2 of 7 ENST00000532059.6 NP_001295022.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GATA4ENST00000532059.6 linkc.531C>T p.Ala177Ala synonymous_variant Exon 2 of 7 1 NM_001308093.3 ENSP00000435712.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.43e-7
AC:
1
AN:
1346010
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
664030
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
27166
American (AMR)
AF:
0.00
AC:
0
AN:
31388
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23672
East Asian (EAS)
AF:
0.00
AC:
0
AN:
31430
South Asian (SAS)
AF:
0.00
AC:
0
AN:
75578
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33200
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3996
European-Non Finnish (NFE)
AF:
9.40e-7
AC:
1
AN:
1063616
Other (OTH)
AF:
0.00
AC:
0
AN:
55964
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
5.1
DANN
Benign
0.96
PhyloP100
-2.3

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

Other links and lift over

dbSNP: rs573733348; hg19: chr8-11566352; API