rs804280
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001308093.3(GATA4):c.1000+56C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,409,926 control chromosomes in the GnomAD database, including 277,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.62 ( 30361 hom., cov: 32)
Exomes 𝑓: 0.62 ( 247456 hom. )
Consequence
GATA4
NM_001308093.3 intron
NM_001308093.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.173
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=-0.84).
BP6
?
Variant 8-11755189-C-A is Benign according to our data. Variant chr8-11755189-C-A is described in ClinVar as [Benign]. Clinvar id is 139596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11755189-C-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA4 | NM_001308093.3 | c.1000+56C>A | intron_variant | ENST00000532059.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA4 | ENST00000532059.6 | c.1000+56C>A | intron_variant | 1 | NM_001308093.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.624 AC: 94843AN: 151966Hom.: 30339 Cov.: 32
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GnomAD4 exome AF: 0.618 AC: 777664AN: 1257842Hom.: 247456 AF XY: 0.622 AC XY: 394900AN XY: 634466
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GnomAD4 genome ? AF: 0.624 AC: 94911AN: 152084Hom.: 30361 Cov.: 32 AF XY: 0.638 AC XY: 47412AN XY: 74356
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Uncertain:1Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
not provided Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | literature only | Molecular Genetics and Enzymology, National Research Centre | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2018 | This variant is associated with the following publications: (PMID: 25928801) - |
Congenital heart disease Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Central Research Laboratory, Sri Devaraj Urs Academy of Higher Education and Research | Jan 07, 2017 | - - |
Atrioventricular septal defect 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
GATA4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 16, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at