rs6983129

chr8-11733627-C-A

Variant summary

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

The NM_001308093.3(GATA4):c.617-15289C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,098 control chromosomes in the GnomAD database, including 21,295 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 0.52 (21295 hom., cov: 33)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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 (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.617-15289C>A		intron_variant		ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.617-15289C>A		intron_variant		1	NM_001308093.3	A1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78502 AN: 151980 Hom.: 21277 Cov.: 33

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.517 AC: 78569 AN: 152098 Hom.: 21295 Cov.: 33 AF XY: 0.505 AC XY: 37567 AN XY: 74352

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.542

Alfa AF: 0.513 Hom.: 42087

Bravo AF: 0.524

Asia WGS AF: 0.234 AC: 821 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	1.3
Dann	Benign	0.53

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: rs6983129; hg19: chr8-11591136;