chr8-11750126-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001308093.3(GATA4):c.802G>A(p.Val268Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
GATA4
NM_001308093.3 missense
NM_001308093.3 missense
Scores
5
6
7
Clinical Significance
Conservation
PhyloP100: 7.93
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.017153054).
BP6
Variant 8-11750126-G-A is Benign according to our data. Variant chr8-11750126-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 472780.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS2
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GATA4 | NM_001308093.3 | c.802G>A | p.Val268Met | missense_variant | 4/7 | ENST00000532059.6 | NP_001295022.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GATA4 | ENST00000532059.6 | c.802G>A | p.Val268Met | missense_variant | 4/7 | 1 | NM_001308093.3 | ENSP00000435712.1 |
Frequencies
GnomAD3 genomes AF: 0.0000919 AC: 14AN: 152280Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.000271 AC: 68AN: 251224Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135848
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GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461742Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 22AN XY: 727190
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GnomAD4 genome AF: 0.0000919 AC: 14AN: 152398Hom.: 0 Cov.: 34 AF XY: 0.0000805 AC XY: 6AN XY: 74526
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 2016 | The p.V267M variant (also known as c.799G>A), located in coding exon 3 of the GATA4 gene, results from a G to A substitution at nucleotide position 799. The valine at codon 267 is replaced by methionine, an amino acid with highly similar properties. In a study of 384 sporadic Chinese patients with congenital heart disease, this alteration was reported in 2 patients and also in 4 of the 957 controls (Wang E et al. PLoS ONE, 2013 Apr;8:e62138). This variant was previously reported in the SNPDatabase as rs116781972. Based on data from ExAC, the A allele was only reported in East Asian population with a frequency of approximately 0.034% (3/8618). Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.54% (1/184) Southern Han Chinese alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Atrioventricular septal defect 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 07, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 06, 2020 | See Variant Classification Assertion Criteria. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
.;.;L;.;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;.
REVEL
Pathogenic
Sift
Benign
T;T;T;T;.
Sift4G
Benign
T;T;D;D;D
Polyphen
0.40
.;.;B;.;.
Vest4
MVP
MPC
1.7
ClinPred
T
GERP RS
Varity_R
gMVP
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