rs11785481

Positions:

• chr8-11759633-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001308093.3(GATA4):​c.*1158C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 152,424 control chromosomes in the GnomAD database, including 946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.098 (946 hom., cov: 33)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: GATA4 NM_001308093.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-11759633-C-T is Benign according to our data. Variant chr8-11759633-C-T is described in ClinVar as [Benign]. Clinvar id is 1281539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11759633-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.*1158C>T		3_prime_UTR_variant	7/7	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.*1158C>T		3_prime_UTR_variant	7/7	1	NM_001308093.3	ENSP00000435712.1
GATA4	ENST00000335135.8	c.*1158C>T		3_prime_UTR_variant	7/7	5		ENSP00000334458.4
GATA4	ENST00000622443.3	c.*1158C>T		3_prime_UTR_variant	8/8	5		ENSP00000482268.2
GATA4	ENST00000528712.5	c.*1158C>T		3_prime_UTR_variant	7/7	2		ENSP00000435043.1

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14871 AN: 152200 Hom.: 945 Cov.: 33

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.0768

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.123 AC: 13 AN: 106 Hom.: 0 Cov.: 0 AF XY: 0.135 AC XY: 10 AN XY: 74

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.0976 AC: 14869 AN: 152318 Hom.: 946 Cov.: 33 AF XY: 0.0939 AC XY: 6991 AN XY: 74470

Gnomad4 AFR AF: 0.0296

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0185

Gnomad4 SAS AF: 0.0441

Gnomad4 FIN AF: 0.0768

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.127

Alfa AF: 0.140 Hom.: 1607

Bravo AF: 0.0979

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11785481; hg19: chr8-11617142;