8-11704219-C-T

Position:

• chr8-11704219-C-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.-543C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,340 control chromosomes in the GnomAD database, including 3,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (3312 hom., cov: 33)
  • Exomes 𝑓: 0.15 (3 hom.)
• Consequence: GATA4 NM_001308093.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.81

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=-0.75).
• BP6: Variant 8-11704219-C-T is Benign according to our data. Variant chr8-11704219-C-T is described in ClinVar as [Benign]. Clinvar id is 1169270.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.-543C>T		5_prime_UTR_variant	1/7	ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.-543C>T		5_prime_UTR_variant	1/7	1	NM_001308093.3	A1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25982 AN: 152112 Hom.: 3309 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.155 AC: 17 AN: 110 Hom.: 3 Cov.: 0 AF XY: 0.144 AC XY: 13 AN XY: 90

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.171 AC: 26013 AN: 152230 Hom.: 3312 Cov.: 33 AF XY: 0.168 AC XY: 12531 AN XY: 74434

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.0842

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.162

Alfa AF: 0.128 Hom.: 269

Bravo AF: 0.178

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atrioventricular septal defect 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.5
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs61277615; hg19: chr8-11561728;