rs804291

Positions:

• chr8-11759062-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000532059.6(GATA4):​c.*587A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 167,288 control chromosomes in the GnomAD database, including 80,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.98 (73264 hom., cov: 31)
  • Exomes 𝑓: 1.0 (7476 hom.)
• Consequence: GATA4 ENST00000532059.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55

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=-0.93).
• BP6: Variant 8-11759062-A-G is Benign according to our data. Variant chr8-11759062-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.*587A>G		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.*587A>G		3_prime_UTR_variant	7/7	1	NM_001308093.3	ENSP00000435712	A1
GATA4	ENST00000335135.8	c.*587A>G		3_prime_UTR_variant	7/7	5		ENSP00000334458	P3
GATA4	ENST00000528712.5	c.*587A>G		3_prime_UTR_variant	7/7	2		ENSP00000435043
GATA4	ENST00000622443.3	c.*587A>G		3_prime_UTR_variant	8/8	5		ENSP00000482268	P3

Frequencies

GnomAD3 genomes AF: 0.980 AC: 149184 AN: 152158 Hom.: 73208 Cov.: 31

Gnomad AFR AF: 0.932

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.986

GnomAD4 exome AF: 0.998 AC: 14982 AN: 15012 Hom.: 7476 Cov.: 0 AF XY: 0.998 AC XY: 7661 AN XY: 7680

Gnomad4 AFR exome AF: 0.925

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.996

GnomAD4 genome AF: 0.980 AC: 149298 AN: 152276 Hom.: 73264 Cov.: 31 AF XY: 0.981 AC XY: 73045 AN XY: 74456

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.994

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.986

Alfa AF: 0.982 Hom.: 10401

Bravo AF: 0.977

Asia WGS AF: 0.997 AC: 3466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.54

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: rs804291; hg19: chr8-11616571;