rs1062219

Positions:

• chr8-11758901-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.*426C>T		3_prime_UTR_variant	7/7	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.*426C>T		3_prime_UTR_variant	7/7	1	NM_001308093.3	ENSP00000435712	A1
GATA4	ENST00000335135.8	c.*426C>T		3_prime_UTR_variant	7/7	5		ENSP00000334458	P3
GATA4	ENST00000528712.5	c.*426C>T		3_prime_UTR_variant	7/7	2		ENSP00000435043
GATA4	ENST00000622443.3	c.*426C>T		3_prime_UTR_variant	8/8	5		ENSP00000482268	P3

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

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.0215

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.381

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

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.0210

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.381

Alfa AF: 0.437 Hom.: 15981

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

Uncertain significance, no assertion criteria provided

literature only

Molecular Genetics and Enzymology, National Research Centre

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.029
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs1062219; hg19: chr8-11616410;