rs867858

Positions:

• chr8-11758829-A-C
• chr8-11758829-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308093.3(GATA4):​c.*354A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 352,036 control chromosomes in the GnomAD database, including 19,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.30 (7205 hom., cov: 32)
  • Exomes 𝑓: 0.34 (11943 hom.)
• Consequence: GATA4 NM_001308093.3 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.602

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.*354A>C		3_prime_UTR_variant	7/7	ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.*354A>C		3_prime_UTR_variant	7/7	1	NM_001308093.3	A1
GATA4	ENST00000335135.8	c.*354A>C		3_prime_UTR_variant	7/7	5		P3
GATA4	ENST00000528712.5	c.*354A>C		3_prime_UTR_variant	7/7	2
GATA4	ENST00000622443.3	c.*354A>C		3_prime_UTR_variant	8/8	5		P3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45519 AN: 151798 Hom.: 7204 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.337 AC: 67505 AN: 200120 Hom.: 11943 Cov.: 0 AF XY: 0.345 AC XY: 37101 AN XY: 107552

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.300 AC: 45528 AN: 151916 Hom.: 7205 Cov.: 32 AF XY: 0.305 AC XY: 22641 AN XY: 74260

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.321

Alfa AF: 0.314 Hom.: 10160

Bravo AF: 0.295

Asia WGS AF: 0.460 AC: 1598 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Molecular Genetics and Enzymology, National Research Centre

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs867858; hg19: chr8-11616338;