rs1390950

Variant names:

• chr8-11738320-C-T
• rs1390950
• NM_001308093.3:c.617-10596C>T

Variant summary

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

The NM_001308093.3(GATA4):​c.617-10596C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,996 control chromosomes in the GnomAD database, including 40,472 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 0.72 (40472 hom., cov: 30)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 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.617-10596C>T		intron	N/A	NP_001295022.1	P43694-2
	GATA4	NM_002052.5		c.617-10599C>T		intron	N/A	NP_002043.2
	GATA4	NM_001308094.2		c.-5-10596C>T		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.617-10596C>T		intron	N/A	ENSP00000435712.1	P43694-2
	GATA4	ENST00000886854.1		c.617-10599C>T		intron	N/A	ENSP00000556913.1
	GATA4	ENST00000886846.1		c.617-10596C>T		intron	N/A	ENSP00000556905.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109390 AN: 151878 Hom.: 40420 Cov.: 30

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.720 AC: 109500 AN: 151996 Hom.: 40472 Cov.: 30 AF XY: 0.719 AC XY: 53393 AN XY: 74268

African (AFR) AF: 0.895 AC: 37132 AN: 41484

American (AMR) AF: 0.655 AC: 10009 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2485 AN: 3470

East Asian (EAS) AF: 0.870 AC: 4498 AN: 5168

South Asian (SAS) AF: 0.683 AC: 3256 AN: 4764

European-Finnish (FIN) AF: 0.614 AC: 6484 AN: 10562

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43401 AN: 67956

Other (OTH) AF: 0.728 AC: 1537 AN: 2110

Alfa AF: 0.658 Hom.: 21953

Bravo AF: 0.730

Asia WGS AF: 0.761 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.37
PhyloP100		-0.21
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: rs1390950; hg19: chr8-11595829;