chr8-11759038-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001308093.3(GATA4):​c.*563C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 172,406 control chromosomes in the GnomAD database, including 15,481 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 13623 hom., cov: 32)
Exomes 𝑓: 0.41 ( 1858 hom. )

Consequence

GATA4
NM_001308093.3 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.622

Publications

23 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: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GATA4NM_001308093.3 linkc.*563C>G 3_prime_UTR_variant Exon 7 of 7 ENST00000532059.6 NP_001295022.1 P43694-2B3KUF4B6DU75

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GATA4ENST00000532059.6 linkc.*563C>G 3_prime_UTR_variant Exon 7 of 7 1 NM_001308093.3 ENSP00000435712.1 P43694-2
GATA4ENST00000335135.8 linkc.*563C>G 3_prime_UTR_variant Exon 7 of 7 5 ENSP00000334458.4 P43694-1
GATA4ENST00000622443.3 linkc.*563C>G 3_prime_UTR_variant Exon 8 of 8 5 ENSP00000482268.2 P43694-1A0A087WZ09
GATA4ENST00000528712.5 linkc.*563C>G 3_prime_UTR_variant Exon 7 of 7 2 ENSP00000435043.1 B3KUF4

Frequencies

GnomAD3 genomes
AF:
0.420
AC:
63802
AN:
151954
Hom.:
13607
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.443
Gnomad AMI
AF:
0.352
Gnomad AMR
AF:
0.388
Gnomad ASJ
AF:
0.489
Gnomad EAS
AF:
0.575
Gnomad SAS
AF:
0.437
Gnomad FIN
AF:
0.387
Gnomad MID
AF:
0.573
Gnomad NFE
AF:
0.401
Gnomad OTH
AF:
0.434
GnomAD4 exome
AF:
0.414
AC:
8413
AN:
20332
Hom.:
1858
Cov.:
0
AF XY:
0.419
AC XY:
4372
AN XY:
10444
show subpopulations
African (AFR)
AF:
0.440
AC:
214
AN:
486
American (AMR)
AF:
0.394
AC:
1166
AN:
2960
Ashkenazi Jewish (ASJ)
AF:
0.452
AC:
133
AN:
294
East Asian (EAS)
AF:
0.579
AC:
770
AN:
1330
South Asian (SAS)
AF:
0.443
AC:
1004
AN:
2268
European-Finnish (FIN)
AF:
0.376
AC:
203
AN:
540
Middle Eastern (MID)
AF:
0.500
AC:
24
AN:
48
European-Non Finnish (NFE)
AF:
0.390
AC:
4459
AN:
11422
Other (OTH)
AF:
0.447
AC:
440
AN:
984
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
219
438
656
875
1094
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
104
208
312
416
520
<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:
0.420
AC:
63867
AN:
152074
Hom.:
13623
Cov.:
32
AF XY:
0.421
AC XY:
31313
AN XY:
74316
show subpopulations
African (AFR)
AF:
0.443
AC:
18383
AN:
41472
American (AMR)
AF:
0.388
AC:
5930
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.489
AC:
1698
AN:
3470
East Asian (EAS)
AF:
0.575
AC:
2963
AN:
5154
South Asian (SAS)
AF:
0.437
AC:
2104
AN:
4818
European-Finnish (FIN)
AF:
0.387
AC:
4093
AN:
10570
Middle Eastern (MID)
AF:
0.585
AC:
172
AN:
294
European-Non Finnish (NFE)
AF:
0.401
AC:
27291
AN:
67986
Other (OTH)
AF:
0.433
AC:
913
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1896
3792
5687
7583
9479
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
606
1212
1818
2424
3030
<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:
0.423
Hom.:
1810
Bravo
AF:
0.418
Asia WGS
AF:
0.510
AC:
1772
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
3.1
DANN
Benign
0.40
PhyloP100
0.62
Mutation Taster
=100/0
polymorphism (auto)

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: rs12825; hg19: chr8-11616547; API