8-11748803-T-C

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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:9

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

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 CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in CliVar as Benign/Likely_benign. Clinvar id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GATA4NM_001308093.3 linkc.617-113T>C intron_variant Intron 2 of 6 ENST00000532059.6 NP_001295022.1 P43694-2B3KUF4B6DU75

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GATA4ENST00000532059.6 linkc.617-113T>C intron_variant Intron 2 of 6 1 NM_001308093.3 ENSP00000435712.1 P43694-2

Frequencies

GnomAD3 genomes
AF:
0.804
AC:
122250
AN:
152134
Hom.:
49742
Cov.:
33
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
0
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
0
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.:
33
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
0
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
0
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

Significance: Benign
Submissions summary: Pathogenic:1Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
Feb 16, 2025
Laboratory of Genetics, Children's Clinical University Hospital Latvia
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Oct 28, 2020
H3Africa Consortium
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:research

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.833, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

-
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

not provided Benign:3
Sep 04, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Congenital heart disease Pathogenic:1Benign:1
Jan 06, 2020
Reproductive Health Research and Development, BGI Genomics
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:curation

NG_008177.2(NM_002052.4):c.617-116T>C in the gene GATA4 has an allele frequency of 0.898 in African subpopulation in the gnomAD database. 128 homozygous occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1, BS2. -

Jan 07, 2017
Central Research Laboratory, Sri Devaraj Urs Academy of Higher Education and Research
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Structural congenital heart disease, multiple types - GATA4 Benign:1
Apr 17, 2023
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.1
DANN
Benign
0.67
PhyloP100
0.33
Mutation Taster
=100/0
disease causing (ClinVar)

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: rs3735819; hg19: chr8-11606312; API