chr8-11742061-A-C

Position:

• chr8-11742061-A-C

Variant summary

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

The NM_001308093.3(GATA4):​c.617-6855A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,954 control chromosomes in the GnomAD database, including 3,993 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 0.18 (3993 hom., cov: 32)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.617-6855A>C		intron_variant		ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.617-6855A>C		intron_variant		1	NM_001308093.3	A1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27920 AN: 151836 Hom.: 3989 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.00661

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.184 AC: 27958 AN: 151954 Hom.: 3993 Cov.: 32 AF XY: 0.195 AC XY: 14473 AN XY: 74274

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.0807

Gnomad4 OTH AF: 0.165

Alfa AF: 0.122 Hom.: 823

Bravo AF: 0.189

Asia WGS AF: 0.466 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.016
DANN	Benign	0.46

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: rs10090884; hg19: chr8-11599570;