rs12156163

chr8-11757260-C-Gchr8-11757260-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001308093.3(GATA4):c.1149+177C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 152,236 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0023 (2 hom., cov: 33)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.59

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-11757260-C-G is Benign according to our data. Variant chr8-11757260-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3042065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00235 (357/152236) while in subpopulation AMR AF= 0.0169 (259/15298). AF 95% confidence interval is 0.0152. There are 2 homozygotes in gnomad4. There are 218 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 357 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.1149+177C>G		intron_variant		ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.1149+177C>G		intron_variant		1	NM_001308093.3	A1

Frequencies

GnomAD3 genomes AF: 0.00235 AC: 357 AN: 152118 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00239

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

GnomAD4 genome AF: 0.00235 AC: 357 AN: 152236 Hom.: 2 Cov.: 33 AF XY: 0.00293 AC XY: 218 AN XY: 74426

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0124

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

GATA4-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.14
Dann	Benign	0.45

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: rs12156163; hg19: chr8-11614769;