rs1062219

Variant names:

• chr8-11758901-C-T
• rs1062219
• NM_001308093.3:c.*426C>T

Variant summary

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

The NM_001308093.3(GATA4):​c.*426C>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 0.347 in 302,428 control chromosomes in the GnomAD database, including 21,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.33 (9740 hom., cov: 32)
  • Exomes 𝑓: 0.37 (11371 hom.)
• Consequence: GATA4 NM_001308093.3 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -2.92
• Publications: 29 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.*426C>T		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.*426C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50036 AN: 151878 Hom.: 9744 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.366 AC: 55030 AN: 150432 Hom.: 11371 Cov.: 0 AF XY: 0.361 AC XY: 28992 AN XY: 80274

African (AFR) AF: 0.171 AC: 810 AN: 4746

American (AMR) AF: 0.244 AC: 1794 AN: 7342

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1963 AN: 3632

East Asian (EAS) AF: 0.0215 AC: 147 AN: 6850

South Asian (SAS) AF: 0.296 AC: 7950 AN: 26862

European-Finnish (FIN) AF: 0.296 AC: 2039 AN: 6888

Middle Eastern (MID) AF: 0.442 AC: 237 AN: 536

European-Non Finnish (NFE) AF: 0.433 AC: 37194 AN: 85966

Other (OTH) AF: 0.381 AC: 2896 AN: 7610

GnomAD4 genome AF: 0.329 AC: 50051 AN: 151996 Hom.: 9740 Cov.: 32 AF XY: 0.317 AC XY: 23540 AN XY: 74286

African (AFR) AF: 0.173 AC: 7176 AN: 41454

American (AMR) AF: 0.286 AC: 4371 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1998 AN: 3468

East Asian (EAS) AF: 0.0210 AC: 108 AN: 5132

South Asian (SAS) AF: 0.292 AC: 1406 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3070 AN: 10596

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30649 AN: 67928

Other (OTH) AF: 0.381 AC: 802 AN: 2104

Alfa AF: 0.429 Hom.: 19954

Bravo AF: 0.321

Asia WGS AF: 0.133 AC: 467 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

-

Molecular Genetics and Enzymology, National Research Centre

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.029
DANN	Benign	0.78
PhyloP100		-2.9
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: rs1062219; hg19: chr8-11616410;