dbSNP rs3735819: GATA4:c.617-113T>C (chr8-11748803-T-C) – 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.617-113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,276,656 control chromosomes in the GnomAD database, including 374,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49802 hom., cov: 33)

Exomes 𝑓: 0.76 ( 324915 hom. )

Consequence

GATA4
NM_001308093.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:8

Conservation

PhyloP100: 0.332

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=-0.87).

BP6

Variant 8-11748803-T-C is Benign according to our data. Variant chr8-11748803-T-C is described in ClinVar as [Benign]. Clinvar id is 433016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11748803-T-C is described in Lovd as [Benign]. Variant chr8-11748803-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3 link	c.617-113T>C		intron_variant	Intron 2 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.617-113T>C		intron_variant	Intron 2 of 6	1	NM_001308093.3	ENSP00000435712.1		P43694-2

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

122250

AN:

152134

Hom.:

49742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.898

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.815

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.984

Gnomad SAS

AF:

0.888

Gnomad FIN

AF:

0.849

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.728

Gnomad OTH

AF:

0.764

GnomAD4 exome

AF:

0.756

AC:

849976

AN:

1124404

Hom.:

324915

AF XY:

0.759

AC XY:

436396

AN XY:

575192

show subpopulations

Gnomad4 AFR exome

AF:

0.905

Gnomad4 AMR exome

AF:

0.859

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.976

Gnomad4 SAS exome

AF:

0.876

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.722

Gnomad4 OTH exome

AF:

0.756

GnomAD4 genome

AF:

0.804

AC:

122370

AN:

152252

Hom.:

49802

Cov.:

AF XY:

0.813

AC XY:

60534

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.898

Gnomad4 AMR

AF:

0.815

Gnomad4 ASJ

AF:

0.635

Gnomad4 EAS

AF:

0.984

Gnomad4 SAS

AF:

0.887

Gnomad4 FIN

AF:

0.849

Gnomad4 NFE

AF:

0.728

Gnomad4 OTH

AF:

0.766

Alfa

AF:

0.752

Hom.:

8823

Bravo

AF:

0.804

Asia WGS

AF:

0.937

AC:

3258

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 28, 2020

H3Africa Consortium

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.833, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital heart disease

Pathogenic:1Benign:1

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

NG_008177.2(NM_002052.4):c.617-116T>C in the gene GATA4 has an allele frequency of 0.898 in African subpopulation in the gnomAD database. 128 homozygous occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1, BS2. -

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

- -

Structural congenital heart disease, multiple types - GATA4

Benign:1

Apr 17, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.1

DANN

Benign

0.67

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