rs884662

Positions:

• chr8-11758992-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-11758992-T-C is Benign according to our data. Variant chr8-11758992-T-C is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.*517T>C		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.*517T>C		3_prime_UTR_variant	7/7	1	NM_001308093.3	ENSP00000435712	A1
GATA4	ENST00000335135.8	c.*517T>C		3_prime_UTR_variant	7/7	5		ENSP00000334458	P3
GATA4	ENST00000528712.5	c.*517T>C		3_prime_UTR_variant	7/7	2		ENSP00000435043
GATA4	ENST00000622443.3	c.*517T>C		3_prime_UTR_variant	8/8	5		ENSP00000482268	P3

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

Gnomad4 AFR exome AF: 0.326

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.299

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

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.309

Alfa AF: 0.319 Hom.: 1342

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

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: rs884662; hg19: chr8-11616501;