8-11754872-T-C

Position:

• chr8-11754872-T-C

Variant summary

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

The ENST00000532059.6(GATA4):​c.913-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,066 control chromosomes in the GnomAD database, including 9,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (9551 hom., cov: 32)
• Consequence: GATA4 ENST00000532059.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53

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=-0.91).
• BP6: Variant 8-11754872-T-C is Benign according to our data. Variant chr8-11754872-T-C is described in ClinVar as [Benign]. Clinvar id is 1271481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.913-174T>C		intron_variant		ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.913-174T>C		intron_variant		1	NM_001308093.3	ENSP00000435712	A1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52868 AN: 151946 Hom.: 9558 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.348 AC: 52887 AN: 152066 Hom.: 9551 Cov.: 32 AF XY: 0.355 AC XY: 26403 AN XY: 74308

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.333

Alfa AF: 0.319 Hom.: 10415

Bravo AF: 0.347

Asia WGS AF: 0.472 AC: 1637 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 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.25

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: rs13273672; hg19: chr8-11612381;