rs1329688744

Variant names:

• chr8-11708627-G-A
• rs1329688744
• NM_001308093.3:c.315G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001308093.3(GATA4):​c.315G>A​(p.Ser105Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,188,774 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: GATA4 NM_001308093.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.634
• Publications: 1 publications found

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]

GATA4 Gene-Disease associations (from GenCC):

• atrial septal defect 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• structural congenital heart disease, multiple types - GATA4

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• testicular anomalies with or without congenital heart disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• metabolic syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• pancreatic hypoplasia-diabetes-congenital heart disease syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• permanent neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• transient neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 8-11708627-G-A is Benign according to our data. Variant chr8-11708627-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 539985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.634 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.315G>A	p.Ser105Ser	synonymous_variant	Exon 2 of 7	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.315G>A	p.Ser105Ser	synonymous_variant	Exon 2 of 7	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000742 AC: 3 AN: 40450 AF XY: 0.0000816

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000306

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000654

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000252 AC: 3 AN: 1188774 Hom.: 0 Cov.: 31 AF XY: 0.00000346 AC XY: 2 AN XY: 577388

African (AFR) AF: 0.00 AC: 0 AN: 24176

American (AMR) AF: 0.000125 AC: 2 AN: 15986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18634

East Asian (EAS) AF: 0.00 AC: 0 AN: 26564

South Asian (SAS) AF: 0.00 AC: 0 AN: 44532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3346

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 979532

Other (OTH) AF: 0.00 AC: 0 AN: 48276

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atrioventricular septal defect 4 Benign:1

Oct 18, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.2
DANN	Benign	0.95
PhyloP100		-0.63

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

Other links and lift over

dbSNP: rs1329688744; hg19: chr8-11566136;