rs904018

Positions:

• chr8-11759007-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.*532T>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 0.61 in 197,636 control chromosomes in the GnomAD database, including 37,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.60 (27918 hom., cov: 32)
  • Exomes 𝑓: 0.63 (9280 hom.)
• Consequence: GATA4 NM_001308093.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

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=-0.94).
• BP6: Variant 8-11759007-T-C is Benign according to our data. Variant chr8-11759007-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.*532T>C		3_prime_UTR_variant	7/7	ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.*532T>C		3_prime_UTR_variant	7/7	1	NM_001308093.3	A1
GATA4	ENST00000335135.8	c.*532T>C		3_prime_UTR_variant	7/7	5		P3
GATA4	ENST00000528712.5	c.*532T>C		3_prime_UTR_variant	7/7	2
GATA4	ENST00000622443.3	c.*532T>C		3_prime_UTR_variant	8/8	5		P3

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91546 AN: 151800 Hom.: 27910 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.635 AC: 29015 AN: 45718 Hom.: 9280 Cov.: 0 AF XY: 0.638 AC XY: 15071 AN XY: 23618

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.710

Gnomad4 EAS exome AF: 0.716

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.597

Gnomad4 NFE exome AF: 0.629

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.603 AC: 91599 AN: 151918 Hom.: 27918 Cov.: 32 AF XY: 0.601 AC XY: 44607 AN XY: 74232

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.621

Alfa AF: 0.629 Hom.: 6090

Bravo AF: 0.597

Asia WGS AF: 0.635 AC: 2207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.34

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: rs904018; hg19: chr8-11616516;