rs4841588

chr8-11756716-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001308093.3(GATA4):c.1001-219G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 612,510 control chromosomes in the GnomAD database, including 18,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3912 hom., cov: 33)
  • Exomes 𝑓: 0.21 (14926 hom.)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0230

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-11756716-G-T is Benign according to our data. Variant chr8-11756716-G-T is described in ClinVar as [Benign]. Clinvar id is 1169507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.1001-219G>T		intron_variant		ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.1001-219G>T		intron_variant		1	NM_001308093.3	A1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29906 AN: 151576 Hom.: 3905 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.211 AC: 97445 AN: 460816 Hom.: 14926 Cov.: 5 AF XY: 0.215 AC XY: 52194 AN XY: 242926

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.659

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.197 AC: 29942 AN: 151694 Hom.: 3912 Cov.: 33 AF XY: 0.209 AC XY: 15514 AN XY: 74096

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.197

Alfa AF: 0.153 Hom.: 521

Bravo AF: 0.198

Asia WGS AF: 0.482 AC: 1670 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Atrioventricular septal defect 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

This variant is associated with the following publications: (PMID: 25928801) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.6
Dann	Benign	0.63

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: rs4841588; hg19: chr8-11614225; COSMIC: COSV58734477; COSMIC: COSV58734477;