rs2645400

Positions:

• chr8-11751907-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308093.3(GATA4):​c.912+1671T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,120 control chromosomes in the GnomAD database, including 6,897 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 0.28 (6897 hom., cov: 32)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.912+1671T>G		intron_variant		ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.912+1671T>G		intron_variant		1	NM_001308093.3	ENSP00000435712	A1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42234 AN: 152002 Hom.: 6896 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.278 AC: 42253 AN: 152120 Hom.: 6897 Cov.: 32 AF XY: 0.283 AC XY: 21025 AN XY: 74354

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.284

Alfa AF: 0.330 Hom.: 5021

Bravo AF: 0.259

Asia WGS AF: 0.356 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.48

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: rs2645400; hg19: chr8-11609416;