8-11703717-A-C

Position:

• chr8-11703717-A-C

Variant summary

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

The ENST00000532977.1(GATA4):​c.-458+2939A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 152,270 control chromosomes in the GnomAD database, including 219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.032 (219 hom., cov: 33)
• Consequence: GATA4 ENST00000532977.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31

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=-0.84).
• BP6: Variant 8-11703717-A-C is Benign according to our data. Variant chr8-11703717-A-C is described in ClinVar as [Benign]. Clinvar id is 1249989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308094.2	c.-6+2939A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532977.1	c.-458+2939A>C		intron_variant		1
GATA4	ENST00000526974.1	c.-458+2939A>C		intron_variant		2
GATA4	ENST00000528712.5	c.-6+2939A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4931 AN: 152152 Hom.: 219 Cov.: 33

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0324 AC: 4930 AN: 152270 Hom.: 219 Cov.: 33 AF XY: 0.0323 AC XY: 2402 AN XY: 74464

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00281

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.000726 Hom.: 0

Bravo AF: 0.0330

Asia WGS AF: 0.0650 AC: 226 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 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs115367741; hg19: chr8-11561226;