Variant chr8-11759731-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001308093.3(GATA4):c.*1256A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,118 control chromosomes in the GnomAD database, including 9,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9410 hom., cov: 33)

Exomes 𝑓: 0.35 ( 4 hom. )

Consequence

GATA4
NM_001308093.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:3

Conservation

PhyloP100: -0.411

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 8-11759731-A-T is Benign according to our data. Variant chr8-11759731-A-T is described in ClinVar as [Benign]. Clinvar id is 433026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11759731-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3 linkuse as main transcript	c.*1256A>T		3_prime_UTR_variant	7/7	ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6 linkuse as main transcript	c.*1256A>T	3_prime_UTR_variant	7/7	1	NM_001308093.3	A1	P43694-2
GATA4	ENST00000335135.8 linkuse as main transcript	c.*1256A>T	3_prime_UTR_variant	7/7	5		P3	P43694-1
GATA4	ENST00000528712.5 linkuse as main transcript	c.*1256A>T	3_prime_UTR_variant	7/7	2
GATA4	ENST00000622443.3 linkuse as main transcript	c.*1256A>T	3_prime_UTR_variant	8/8	5		P3	P43694-1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52820

AN:

151896

Hom.:

9401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.364

GnomAD4 exome

AF:

0.346

AC:

AN:

104

Hom.:

Cov.:

AF XY:

0.368

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.346

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.348

AC:

52863

AN:

152014

Hom.:

9410

Cov.:

AF XY:

0.350

AC XY:

25984

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.382

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.537

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.295

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.363

Alfa

AF:

0.335

Hom.:

5036

Bravo

AF:

0.351

Asia WGS

AF:

0.462

AC:

1602

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital heart disease

Pathogenic:1Benign:1

Benign, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NM_002052.3:c.*1256A>T in the gene GATA4 has an allele frequency of 0.376 in African subpopulation in the gnomAD database. 1936 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 specified

Benign:1

Benign, criteria provided, single submitter

research

H3Africa Consortium

Oct 28, 2020

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.375, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.2

DANN

Benign

0.75

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

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