rs804290

Positions:

• chr8-11759327-G-A
• chr8-11759327-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000532059.6(GATA4):​c.*852G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,750 control chromosomes in the GnomAD database, including 2,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2607 hom., cov: 33)
  • Exomes 𝑓: 0.20 (17 hom.)
• Consequence: GATA4 ENST00000532059.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:4
• Conservation: PhyloP100: -0.935

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-11759327-G-A is Benign according to our data. Variant chr8-11759327-G-A is described in ClinVar as [Benign]. Clinvar id is 433024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11759327-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.*852G>A		3_prime_UTR_variant	7/7	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.*852G>A		3_prime_UTR_variant	7/7	1	NM_001308093.3	ENSP00000435712	A1
GATA4	ENST00000335135.8	c.*852G>A		3_prime_UTR_variant	7/7	5		ENSP00000334458	P3
GATA4	ENST00000528712.5	c.*852G>A		3_prime_UTR_variant	7/7	2		ENSP00000435043
GATA4	ENST00000622443.3	c.*852G>A		3_prime_UTR_variant	8/8	5		ENSP00000482268	P3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24477 AN: 152116 Hom.: 2614 Cov.: 33

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.202 AC: 104 AN: 516 Hom.: 17 Cov.: 0 AF XY: 0.210 AC XY: 77 AN XY: 366

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.161 AC: 24465 AN: 152234 Hom.: 2607 Cov.: 33 AF XY: 0.153 AC XY: 11413 AN XY: 74428

Gnomad4 AFR AF: 0.0477

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.184

Alfa AF: 0.212 Hom.: 4065

Bravo AF: 0.155

Asia WGS AF: 0.0760 AC: 267 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital heart disease Pathogenic:1 Benign:1

Pathogenic, no assertion criteria provided	clinical testing	Central Research Laboratory, Sri Devaraj Urs Academy of Higher Education and Research	Jan 07, 2017	- -
Benign, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NM_002052.3:c.*852G>A in the gene GATA4 has an allele frequency of 0.228 in European (non-Finnish) subpopulation in the gnomAD database. 460 homozygous occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1; BS2. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

GATA4-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 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

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs804290; hg19: chr8-11616836;