rs1062270

Positions:

• chr8-11759830-G-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.*1355G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 152,532 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (255 hom., cov: 33)
  • Exomes 𝑓: 0.060 (0 hom.)
• Consequence: GATA4 NM_001308093.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63

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=-0.54).
• BP6: Variant 8-11759830-G-A is Benign according to our data. Variant chr8-11759830-G-A is described in ClinVar as [Benign]. Clinvar id is 1244459.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-11759830-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.*1355G>A		3_prime_UTR_variant	7/7	ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.*1355G>A		3_prime_UTR_variant	7/7	1	NM_001308093.3	A1
GATA4	ENST00000335135.8	c.*1355G>A		3_prime_UTR_variant	7/7	5		P3
GATA4	ENST00000528712.5	c.*1355G>A		3_prime_UTR_variant	7/7	2
GATA4	ENST00000622443.3	c.*1355G>A		3_prime_UTR_variant	8/8	5		P3

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7256 AN: 152164 Hom.: 255 Cov.: 33

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0449

GnomAD4 exome AF: 0.0600 AC: 15 AN: 250 Hom.: 0 Cov.: 0 AF XY: 0.0811 AC XY: 12 AN XY: 148

Gnomad4 FIN exome AF: 0.0565

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.0477 AC: 7257 AN: 152282 Hom.: 255 Cov.: 33 AF XY: 0.0468 AC XY: 3480 AN XY: 74438

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.0528

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.0659

Gnomad4 NFE AF: 0.0679

Gnomad4 OTH AF: 0.0444

Alfa AF: 0.0621 Hom.: 57

Bravo AF: 0.0472

Asia WGS AF: 0.00549 AC: 20 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

May 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1062270; hg19: chr8-11617339; COSMIC: COSV100632913; COSMIC: COSV100632913;