dbSNP rs804280: GATA4:c.1000+56C>A (chr8-11755189-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001308093.3(GATA4):c.1000+56C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,409,926 control chromosomes in the GnomAD database, including 277,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30361 hom., cov: 32)

Exomes 𝑓: 0.62 ( 247456 hom. )

Consequence

GATA4
NM_001308093.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1U:1B:9

Conservation

PhyloP100: -0.173

Variant links:

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]

GATA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-11755189-C-A is Benign according to our data. Variant chr8-11755189-C-A is described in ClinVar as [Benign]. Clinvar id is 139596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11755189-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3 link	c.1000+56C>A		intron_variant	Intron 5 of 6	ENST00000532059.6	NP_001295022.1	P43694-2B3KUF4B6DU75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6 link	c.1000+56C>A		intron_variant	Intron 5 of 6	1	NM_001308093.3	ENSP00000435712.1		P43694-2

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94843

AN:

151966

Hom.:

30339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.588

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.981

Gnomad SAS

AF:

0.825

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.581

Gnomad OTH

AF:

0.611

GnomAD4 exome

AF:

0.618

AC:

777664

AN:

1257842

Hom.:

247456

AF XY:

0.622

AC XY:

394900

AN XY:

634466

show subpopulations

Gnomad4 AFR exome

AF:

0.581

Gnomad4 AMR exome

AF:

0.789

Gnomad4 ASJ exome

AF:

0.437

Gnomad4 EAS exome

AF:

0.975

Gnomad4 SAS exome

AF:

0.805

Gnomad4 FIN exome

AF:

0.695

Gnomad4 NFE exome

AF:

0.582

Gnomad4 OTH exome

AF:

0.613

GnomAD4 genome

AF:

0.624

AC:

94911

AN:

152084

Hom.:

30361

Cov.:

AF XY:

0.638

AC XY:

47412

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.587

Gnomad4 AMR

AF:

0.713

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.980

Gnomad4 SAS

AF:

0.823

Gnomad4 FIN

AF:

0.718

Gnomad4 NFE

AF:

0.581

Gnomad4 OTH

AF:

0.615

Alfa

AF:

0.590

Hom.:

34998

Bravo

AF:

0.623

Asia WGS

AF:

0.888

AC:

3086

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Uncertain:1Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Uncertain:1Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Molecular Genetics and Enzymology, National Research Centre

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 25928801) -

Congenital heart disease

Pathogenic:1

Jan 07, 2017

Central Research Laboratory, Sri Devaraj Urs Academy of Higher Education and Research

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Atrioventricular septal defect 4

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GATA4-related disorder

Benign:1

Feb 16, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.84

CADD

Benign

0.56

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over