chr8-11759038-C-G

Variant names:

• chr8-11759038-C-G
• rs12825
• NM_001308093.3:c.*563C>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.*563C>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 0.419 in 172,406 control chromosomes in the GnomAD database, including 15,481 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 0.42 (13623 hom., cov: 32)
  • Exomes 𝑓: 0.41 (1858 hom.)
• Consequence: GATA4 NM_001308093.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622
• Publications: 23 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.*563C>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.*563C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001308093.3	ENSP00000435712.1
GATA4	ENST00000335135.8	c.*563C>G		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000334458.4
GATA4	ENST00000622443.3	c.*563C>G		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000482268.2
GATA4	ENST00000528712.5	c.*563C>G		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000435043.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63802 AN: 151954 Hom.: 13607 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.414 AC: 8413 AN: 20332 Hom.: 1858 Cov.: 0 AF XY: 0.419 AC XY: 4372 AN XY: 10444

African (AFR) AF: 0.440 AC: 214 AN: 486

American (AMR) AF: 0.394 AC: 1166 AN: 2960

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 133 AN: 294

East Asian (EAS) AF: 0.579 AC: 770 AN: 1330

South Asian (SAS) AF: 0.443 AC: 1004 AN: 2268

European-Finnish (FIN) AF: 0.376 AC: 203 AN: 540

Middle Eastern (MID) AF: 0.500 AC: 24 AN: 48

European-Non Finnish (NFE) AF: 0.390 AC: 4459 AN: 11422

Other (OTH) AF: 0.447 AC: 440 AN: 984

GnomAD4 genome AF: 0.420 AC: 63867 AN: 152074 Hom.: 13623 Cov.: 32 AF XY: 0.421 AC XY: 31313 AN XY: 74316

African (AFR) AF: 0.443 AC: 18383 AN: 41472

American (AMR) AF: 0.388 AC: 5930 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1698 AN: 3470

East Asian (EAS) AF: 0.575 AC: 2963 AN: 5154

South Asian (SAS) AF: 0.437 AC: 2104 AN: 4818

European-Finnish (FIN) AF: 0.387 AC: 4093 AN: 10570

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27291 AN: 67986

Other (OTH) AF: 0.433 AC: 913 AN: 2110

Alfa AF: 0.423 Hom.: 1810

Bravo AF: 0.418

Asia WGS AF: 0.510 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.40
PhyloP100		0.62
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: rs12825; hg19: chr8-11616547;