rs755482369

chr8-11756969-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001308093.3(GATA4):c.1035C>T(p.Ser345=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: GATA4 NM_001308093.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.34

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 8-11756969-C-T is Benign according to our data. Variant chr8-11756969-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 539988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.34 with no splicing effect.
• BS2: High AC in GnomAdExome at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA4	NM_001308093.3	c.1035C>T	p.Ser345=	synonymous_variant	6/7	ENST00000532059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA4	ENST00000532059.6	c.1035C>T	p.Ser345=	synonymous_variant	6/7	1	NM_001308093.3	A1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152266 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000398 AC: 10 AN: 251412 Hom.: 0 AF XY: 0.0000442 AC XY: 6 AN XY: 135890

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74396

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Atrioventricular septal defect 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 22, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	6.3
Dann	Benign	0.68

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: rs755482369; hg19: chr8-11614478; COSMIC: COSV58732917; COSMIC: COSV58732917;