rs3735819

Variant summary

Our verdict is Benign. Variant got -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 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:7

Conservation

PhyloP100: 0.332
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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]. 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 Lovd as [Benign]. Variant chr8-11748803-T-C is described in Lovd as [Likely_benign].
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
Gnomad4 AFR exome
AF:
0.905
Gnomad4 AMR exome
AF:
0.859
Gnomad4 ASJ exome
AF:
0.643
Gnomad4 EAS exome
AF:
0.976
Gnomad4 SAS exome
AF:
0.876
Gnomad4 FIN exome
AF:
0.833
Gnomad4 NFE exome
AF:
0.722
Gnomad4 OTH exome
AF:
0.756
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
Gnomad4 AFR
AF:
0.898
Gnomad4 AMR
AF:
0.815
Gnomad4 ASJ
AF:
0.635
Gnomad4 EAS
AF:
0.984
Gnomad4 SAS
AF:
0.887
Gnomad4 FIN
AF:
0.849
Gnomad4 NFE
AF:
0.728
Gnomad4 OTH
AF:
0.766
Alfa
AF:
0.752
Hom.:
8823
Bravo
AF:
0.804
Asia WGS
AF:
0.937
AC:
3258
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Pathogenic:1Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
-
Genome Diagnostics Laboratory, Amsterdam University Medical Center
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. -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
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

- -

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

- -

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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.1
DANN
Benign
0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3735819; hg19: chr8-11606312; API