rs884662

Variant names:

• chr8-11758992-T-C
• rs884662
• NM_001308093.3:c.*517T>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.*517T>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 0.31 in 206,004 control chromosomes in the GnomAD database, including 10,294 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 0.32 (7716 hom., cov: 31)
  • Exomes 𝑓: 0.29 (2578 hom.)
• Consequence: GATA4 NM_001308093.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.*517T>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.*517T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47957 AN: 151804 Hom.: 7704 Cov.: 31

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.294 AC: 15874 AN: 54082 Hom.: 2578 Cov.: 0 AF XY: 0.292 AC XY: 8142 AN XY: 27896

African (AFR) AF: 0.326 AC: 664 AN: 2034

American (AMR) AF: 0.266 AC: 990 AN: 3722

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 466 AN: 1218

East Asian (EAS) AF: 0.151 AC: 532 AN: 3512

South Asian (SAS) AF: 0.265 AC: 1643 AN: 6190

European-Finnish (FIN) AF: 0.276 AC: 539 AN: 1950

Middle Eastern (MID) AF: 0.295 AC: 59 AN: 200

European-Non Finnish (NFE) AF: 0.313 AC: 10139 AN: 32444

Other (OTH) AF: 0.299 AC: 842 AN: 2812

GnomAD4 genome AF: 0.316 AC: 48001 AN: 151922 Hom.: 7716 Cov.: 31 AF XY: 0.309 AC XY: 22913 AN XY: 74252

African (AFR) AF: 0.341 AC: 14123 AN: 41394

American (AMR) AF: 0.272 AC: 4155 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1421 AN: 3468

East Asian (EAS) AF: 0.168 AC: 864 AN: 5148

South Asian (SAS) AF: 0.267 AC: 1288 AN: 4822

European-Finnish (FIN) AF: 0.292 AC: 3082 AN: 10562

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22187 AN: 67942

Other (OTH) AF: 0.309 AC: 649 AN: 2100

Alfa AF: 0.315 Hom.: 2390

Bravo AF: 0.317

Asia WGS AF: 0.180 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.61
PhyloP100		-0.79
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: rs884662; hg19: chr8-11616501;