rs904018

Variant names:

• chr8-11759007-T-C
• rs904018
• NM_001308093.3:c.*532T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308093.3(GATA4):​c.*532T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 197,636 control chromosomes in the GnomAD database, including 37,198 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27918 hom., cov: 32)
  • Exomes 𝑓: 0.63 (9280 hom.)
• Consequence: GATA4 NM_001308093.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 16 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.*532T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.*532T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91546 AN: 151800 Hom.: 27910 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.635 AC: 29015 AN: 45718 Hom.: 9280 Cov.: 0 AF XY: 0.638 AC XY: 15071 AN XY: 23618

African (AFR) AF: 0.534 AC: 873 AN: 1634

American (AMR) AF: 0.596 AC: 2152 AN: 3608

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 692 AN: 974

East Asian (EAS) AF: 0.716 AC: 2274 AN: 3174

South Asian (SAS) AF: 0.669 AC: 3447 AN: 5152

European-Finnish (FIN) AF: 0.597 AC: 907 AN: 1520

Middle Eastern (MID) AF: 0.706 AC: 120 AN: 170

European-Non Finnish (NFE) AF: 0.629 AC: 17028 AN: 27090

Other (OTH) AF: 0.635 AC: 1522 AN: 2396

GnomAD4 genome AF: 0.603 AC: 91599 AN: 151918 Hom.: 27918 Cov.: 32 AF XY: 0.601 AC XY: 44607 AN XY: 74232

African (AFR) AF: 0.522 AC: 21632 AN: 41428

American (AMR) AF: 0.579 AC: 8852 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2591 AN: 3472

East Asian (EAS) AF: 0.727 AC: 3728 AN: 5126

South Asian (SAS) AF: 0.654 AC: 3150 AN: 4816

European-Finnish (FIN) AF: 0.596 AC: 6285 AN: 10546

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43410 AN: 67928

Other (OTH) AF: 0.621 AC: 1311 AN: 2110

Alfa AF: 0.625 Hom.: 10126

Bravo AF: 0.597

Asia WGS AF: 0.635 AC: 2207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.34
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs904018; hg19: chr8-11616516;