rs1062215
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001308093.3(GATA4):c.726C>T(p.Cys242=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,614,220 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 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
GATA4
NM_001308093.3 synonymous
NM_001308093.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.682
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 8-11749025-C-T is Benign according to our data. Variant chr8-11749025-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 264047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.682 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000276 (42/152344) while in subpopulation EAS AF= 0.00444 (23/5186). AF 95% confidence interval is 0.00303. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 42 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA4 | NM_001308093.3 | c.726C>T | p.Cys242= | synonymous_variant | 3/7 | ENST00000532059.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA4 | ENST00000532059.6 | c.726C>T | p.Cys242= | synonymous_variant | 3/7 | 1 | NM_001308093.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152226Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000398 AC: 100AN: 251468Hom.: 1 AF XY: 0.000346 AC XY: 47AN XY: 135912
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GnomAD4 exome AF: 0.000160 AC: 234AN: 1461876Hom.: 1 Cov.: 32 AF XY: 0.000154 AC XY: 112AN XY: 727244
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GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Atrioventricular septal defect 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 17, 2020 | This variant is associated with the following publications: (PMID: 29325903, 20874241, 18672102, 20659440) - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2015 | 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
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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