rs12825

Variant names:

• chr8-11759038-C-G
• rs12825
• NM_001308093.3:c.*563C>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 8-11759038-C-G is Benign according to our data. Variant chr8-11759038-C-G is described in Lovd as [Benign].
• 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

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.447

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

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.433

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12825; hg19: chr8-11616547;