8-11689641-T-C

Position:

• chr8-11689641-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000532977.1(GATA4):​c.-725-10870T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,080 control chromosomes in the GnomAD database, including 25,188 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (25188 hom., cov: 32)
• Consequence: GATA4 ENST00000532977.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA4	NM_001308094.2	c.-273-10870T>C		intron_variant			NP_001295023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532977.1	c.-725-10870T>C		intron_variant		1		ENSP00000473671
GATA4	ENST00000528712.5	c.-273-10870T>C		intron_variant		2		ENSP00000435043

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82614 AN: 151962 Hom.: 25189 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.543 AC: 82643 AN: 152080 Hom.: 25188 Cov.: 32 AF XY: 0.547 AC XY: 40672 AN XY: 74316

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.570

Alfa AF: 0.641 Hom.: 50036

Bravo AF: 0.523

Asia WGS AF: 0.645 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2409809; hg19: chr8-11547150;