rs192122549
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001308093.3(GATA4):c.630C>T(p.Asp210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,614,210 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 1 hom. )
Consequence
GATA4
NM_001308093.3 synonymous
NM_001308093.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.53
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 8-11748929-C-T is Benign according to our data. Variant chr8-11748929-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 239101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748929-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.53 with no splicing effect.
BS2
?
High AC in GnomAd4 at 31 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA4 | NM_001308093.3 | c.630C>T | p.Asp210= | synonymous_variant | 3/7 | ENST00000532059.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA4 | ENST00000532059.6 | c.630C>T | p.Asp210= | synonymous_variant | 3/7 | 1 | NM_001308093.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000330 AC: 83AN: 251486Hom.: 0 AF XY: 0.000294 AC XY: 40AN XY: 135920
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GnomAD4 exome AF: 0.000300 AC: 438AN: 1461872Hom.: 1 Cov.: 32 AF XY: 0.000279 AC XY: 203AN XY: 727242
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GnomAD4 genome ? AF: 0.000203 AC: 31AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 22, 2021 | This variant is associated with the following publications: (PMID: 27374936) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | GATA4: BP4 - |
Atrioventricular septal defect 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 14, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 11
Find out detailed SpliceAI scores and Pangolin per-transcript scores at