8-11757260-C-T

Variant names:

• chr8-11757260-C-T
• rs12156163
• NM_001308093.3:c.1149+177C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001308093.3(GATA4):​c.1149+177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,210 control chromosomes in the GnomAD database, including 2,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2479 hom., cov: 33)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Benign criteria provided, single submitter P:1 B:4
• 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=-0.87).
• BP6: Variant 8-11757260-C-T is Benign according to our data. Variant chr8-11757260-C-T is described in ClinVar as [Benign]. Clinvar id is 433023.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-11757260-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.1149+177C>T		intron_variant	Intron 6 of 6	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.1149+177C>T		intron_variant	Intron 6 of 6	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23892 AN: 152092 Hom.: 2486 Cov.: 33

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.157 AC: 23879 AN: 152210 Hom.: 2479 Cov.: 33 AF XY: 0.150 AC XY: 11155 AN XY: 74412

Gnomad4 AFR AF: 0.0468

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.182

Alfa AF: 0.0946 Hom.: 142

Bravo AF: 0.152

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:4

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital heart disease Pathogenic:1 Benign:1

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

NG_008177.2(NM_002052.4):c.1146+177C>T in the gene GATA4 has an allele frequency of 0.223 in European (non-Finnish) subpopulation in the gnomAD database. 435 homozygous occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1; BS2. -

Jan 07, 2017

Central Research Laboratory, Sri Devaraj Urs Academy of Higher Education and Research

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:2

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.63

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;