chr8-11733627-C-A

Variant names:

• chr8-11733627-C-A
• rs6983129
• NM_001308093.3:c.617-15289C>A

Variant summary

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

The NM_001308093.3(GATA4):​c.617-15289C>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
• Publications: 21 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308093.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA4	NM_001308093.3	MANE Select	c.617-15289C>A		intron	N/A	NP_001295022.1	P43694-2
	GATA4	NM_002052.5		c.617-15292C>A		intron	N/A	NP_002043.2
	GATA4	NM_001308094.2		c.-5-15289C>A		intron	N/A	NP_001295023.1	B3KUF4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA4	ENST00000532059.6	TSL:1 MANE Select	c.617-15289C>A		intron	N/A	ENSP00000435712.1	P43694-2
	GATA4	ENST00000886854.1		c.617-15292C>A		intron	N/A	ENSP00000556913.1
	GATA4	ENST00000886846.1		c.617-15289C>A		intron	N/A	ENSP00000556905.1

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

African (AFR) AF: 0.629 AC: 26093 AN: 41498

American (AMR) AF: 0.434 AC: 6626 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2200 AN: 3466

East Asian (EAS) AF: 0.125 AC: 648 AN: 5176

South Asian (SAS) AF: 0.326 AC: 1573 AN: 4820

European-Finnish (FIN) AF: 0.420 AC: 4432 AN: 10562

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35229 AN: 67972

Other (OTH) AF: 0.542 AC: 1146 AN: 2116

Alfa AF: 0.512 Hom.: 90009

Bravo AF: 0.524

Asia WGS AF: 0.234 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		0.025
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: rs6983129; hg19: chr8-11591136;