chr8-11757212-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001308093.3(GATA4):c.1149+129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0036 in 1,375,922 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 34 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 49 hom. )

Consequence

GATA4
NM_001308093.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.78

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

atrial septal defect 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
structural congenital heart disease, multiple types - GATA4
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
testicular anomalies with or without congenital heart disease
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
metabolic syndrome
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
neonatal diabetes mellitus
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
pancreatic hypoplasia-diabetes-congenital heart disease syndrome
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
permanent neonatal diabetes mellitus
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
transient neonatal diabetes mellitus
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
46,XY partial gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tetralogy of fallot
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

GATA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-11757212-C-T is Benign according to our data. Variant chr8-11757212-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 433022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1695/152344) while in subpopulation AFR AF = 0.0352 (1462/41570). AF 95% confidence interval is 0.0337. There are 34 homozygotes in GnomAd4. There are 866 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1695 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3 link	c.1149+129C>T		intron_variant	Intron 6 of 6	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6 link	c.1149+129C>T		intron_variant	Intron 6 of 6	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1695

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00365

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00267

AC:

3263

AN:

1223578

Hom.:

AF XY:

0.00306

AC XY:

1839

AN XY:

600356

show subpopulations

African (AFR)

AF:

0.0392

AC:

1096

AN:

27932

American (AMR)

AF:

0.00171

AC:

AN:

29282

Ashkenazi Jewish (ASJ)

AF:

0.000887

AC:

AN:

20296

East Asian (EAS)

AF:

0.00800

AC:

277

AN:

34604

South Asian (SAS)

AF:

0.0216

AC:

1430

AN:

66334

European-Finnish (FIN)

AF:

0.0000502

AC:

AN:

39868

Middle Eastern (MID)

AF:

0.00335

AC:

AN:

3584

European-Non Finnish (NFE)

AF:

0.000175

AC:

166

AN:

950216

Other (OTH)

AF:

0.00412

AC:

212

AN:

51462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

180

359

539

718

898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0111

AC:

1695

AN:

152344

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

866

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0352

AC:

1462

AN:

41570

American (AMR)

AF:

0.00412

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00366

AC:

AN:

5188

South Asian (SAS)

AF:

0.0219

AC:

106

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68030

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

178

266

355

444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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.1146+129C>T in the GATA4 gene has an allele frequency of 0.034 in African subpopulation in the gnomAD database. 8 homozygous occurrences are observed in the gnomAD database. Benign computational verdict because benign prediction from DANN. Taken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1, BS2, BP4. -

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

- -

not specified

Benign:1

Nov 09, 2021

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1146+129C>T variant in GATA4 is classified as benign because it has been identified in 3.38% (294/8710) of African/African-American chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP codes applied: BA1 -

not provided

Benign:1

Sep 11, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.2

(source)

DANN

Benign

0.64

PhyloP100

-2.8

Mutation Taster

=100/0

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over