8-11735524-T-G

Variant names:

• chr8-11735524-T-G
• rs13259242
• NM_001308093.3:c.617-13392T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308093.3(GATA4):​c.617-13392T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,262 control chromosomes in the GnomAD database, including 9,995 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 0.32 (9995 hom., cov: 34)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 9 publications found

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]

GATA4 Gene-Disease associations (from GenCC):

• atrial septal defect 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• structural congenital heart disease, multiple types - GATA4

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• testicular anomalies with or without congenital heart disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• metabolic syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• pancreatic hypoplasia-diabetes-congenital heart disease syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• permanent neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• transient neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.617-13392T>G		intron_variant	Intron 2 of 6	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.617-13392T>G		intron_variant	Intron 2 of 6	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48521 AN: 152144 Hom.: 9997 Cov.: 34

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.319 AC: 48511 AN: 152262 Hom.: 9995 Cov.: 34 AF XY: 0.309 AC XY: 22985 AN XY: 74446

African (AFR) AF: 0.0916 AC: 3807 AN: 41552

American (AMR) AF: 0.320 AC: 4889 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1885 AN: 3470

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5188

South Asian (SAS) AF: 0.179 AC: 866 AN: 4830

European-Finnish (FIN) AF: 0.351 AC: 3715 AN: 10594

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31910 AN: 68016

Other (OTH) AF: 0.367 AC: 774 AN: 2110

Alfa AF: 0.273 Hom.: 783

Bravo AF: 0.308

Asia WGS AF: 0.104 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.66
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13259242; hg19: chr8-11593033;