rs804291

Variant names:

• chr8-11759062-A-G
• rs804291
• NM_001308093.3:c.*587A>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.*587A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 167,288 control chromosomes in the GnomAD database, including 80,740 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 0.98 (73264 hom., cov: 31)
  • Exomes 𝑓: 1.0 (7476 hom.)
• Consequence: GATA4 NM_001308093.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 7 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 (SAS) allele frequency at 95% confidence interval = 0.993 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA4	NM_001308093.3	MANE Select	c.*587A>G		3_prime_UTR	Exon 7 of 7	NP_001295022.1
	GATA4	NM_002052.5		c.*587A>G		3_prime_UTR	Exon 7 of 7	NP_002043.2
	GATA4	NM_001308094.2		c.*587A>G		3_prime_UTR	Exon 7 of 7	NP_001295023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA4	ENST00000532059.6	TSL:1 MANE Select	c.*587A>G		3_prime_UTR	Exon 7 of 7	ENSP00000435712.1
	GATA4	ENST00000335135.8	TSL:5	c.*587A>G		3_prime_UTR	Exon 7 of 7	ENSP00000334458.4
	GATA4	ENST00000622443.3	TSL:5	c.*587A>G		3_prime_UTR	Exon 8 of 8	ENSP00000482268.2

Frequencies

GnomAD3 genomes AF: 0.980 AC: 149184 AN: 152158 Hom.: 73208 Cov.: 31

Gnomad AFR AF: 0.932

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.986

GnomAD4 exome AF: 0.998 AC: 14982 AN: 15012 Hom.: 7476 Cov.: 0 AF XY: 0.998 AC XY: 7661 AN XY: 7680

African (AFR) AF: 0.925 AC: 209 AN: 226

American (AMR) AF: 0.997 AC: 2575 AN: 2582

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 170 AN: 170

East Asian (EAS) AF: 1.00 AC: 752 AN: 752

South Asian (SAS) AF: 1.00 AC: 1656 AN: 1656

European-Finnish (FIN) AF: 1.00 AC: 366 AN: 366

Middle Eastern (MID) AF: 1.00 AC: 40 AN: 40

European-Non Finnish (NFE) AF: 1.00 AC: 8477 AN: 8480

Other (OTH) AF: 0.996 AC: 737 AN: 740

GnomAD4 genome AF: 0.980 AC: 149298 AN: 152276 Hom.: 73264 Cov.: 31 AF XY: 0.981 AC XY: 73045 AN XY: 74456

African (AFR) AF: 0.932 AC: 38712 AN: 41538

American (AMR) AF: 0.994 AC: 15197 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5162 AN: 5164

South Asian (SAS) AF: 1.00 AC: 4826 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68020 AN: 68044

Other (OTH) AF: 0.986 AC: 2084 AN: 2114

Alfa AF: 0.982 Hom.: 10401

Bravo AF: 0.977

Asia WGS AF: 0.997 AC: 3466 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	0.10
DANN	Benign	0.54
PhyloP100		-2.6
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: rs804291; hg19: chr8-11616571;