chr8-11707578-C-A

Position:

• chr8-11707578-C-A

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.-457-278C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,072 control chromosomes in the GnomAD database, including 4,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4322 hom., cov: 32)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.292

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 8-11707578-C-A is Benign according to our data. Variant chr8-11707578-C-A is described in ClinVar as [Benign]. Clinvar id is 1236492.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.-457-278C>A		intron_variant		ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.-457-278C>A		intron_variant		1	NM_001308093.3	A1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31608 AN: 151954 Hom.: 4309 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.208 AC: 31666 AN: 152072 Hom.: 4322 Cov.: 32 AF XY: 0.204 AC XY: 15182 AN XY: 74344

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.207

Alfa AF: 0.156 Hom.: 1185

Bravo AF: 0.216

Asia WGS AF: 0.184 AC: 643 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.93
DANN	Benign	0.74

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: rs10088151; hg19: chr8-11565087; COSMIC: COSV58735094; COSMIC: COSV58735094;