rs3729851

Positions:

• chr8-11755333-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001308093.3(GATA4):​c.1000+200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 152,242 control chromosomes in the GnomAD database, including 911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.093 (911 hom., cov: 32)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Benign criteria provided, single submitter P:1 B:2
• Conservation: PhyloP100: -0.0290

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-11755333-G-A is Benign according to our data. Variant chr8-11755333-G-A is described in ClinVar as [Benign]. Clinvar id is 433020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.1000+200G>A		intron_variant		ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.1000+200G>A		intron_variant		1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14191 AN: 152124 Hom.: 915 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0883

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0676

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0932 AC: 14185 AN: 152242 Hom.: 911 Cov.: 32 AF XY: 0.0880 AC XY: 6547 AN XY: 74436

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.0883

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0675

Gnomad4 FIN AF: 0.0813

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.106

Alfa AF: 0.126 Hom.: 586

Bravo AF: 0.0905

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital heart disease Pathogenic:1 Benign:1

Benign, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NG_008177.2(NM_002052.4):c.997+200G>A in the gene GATA4 has an allele frequency of 0.138 in European (non-Finnish) subpopulation in the gnomAD database. 152 homozygous occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1, BS2. -
Pathogenic, no assertion criteria provided	clinical testing	Central Research Laboratory, Sri Devaraj Urs Academy of Higher Education and Research	Jan 07, 2017	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.48

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: rs3729851; hg19: chr8-11612842;