NM_001308093.3:c.912+245G>A

Variant names:

• chr8-11750481-G-A
• rs7006733
• NM_001308093.3:c.912+245G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001308093.3(GATA4):​c.912+245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,228 control chromosomes in the GnomAD database, including 43,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (43086 hom., cov: 33)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54
• Publications: 13 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 8-11750481-G-A is Benign according to our data. Variant chr8-11750481-G-A is described in ClinVar as Benign. ClinVar VariationId is 1293502.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308093.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA4	NM_001308093.3	MANE Select	c.912+245G>A		intron	N/A	NP_001295022.1
	GATA4	NM_002052.5		c.909+245G>A		intron	N/A	NP_002043.2
	GATA4	NM_001308094.2		c.291+245G>A		intron	N/A	NP_001295023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA4	ENST00000532059.6	TSL:1 MANE Select	c.912+245G>A		intron	N/A	ENSP00000435712.1
	GATA4	ENST00000335135.8	TSL:5	c.909+245G>A		intron	N/A	ENSP00000334458.4
	GATA4	ENST00000622443.3	TSL:5	c.909+245G>A		intron	N/A	ENSP00000482268.2

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113005 AN: 152108 Hom.: 43031 Cov.: 33

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.693

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.743 AC: 113120 AN: 152228 Hom.: 43086 Cov.: 33 AF XY: 0.754 AC XY: 56118 AN XY: 74412

African (AFR) AF: 0.871 AC: 36184 AN: 41542

American (AMR) AF: 0.771 AC: 11786 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1984 AN: 3468

East Asian (EAS) AF: 0.982 AC: 5099 AN: 5194

South Asian (SAS) AF: 0.783 AC: 3779 AN: 4824

European-Finnish (FIN) AF: 0.798 AC: 8457 AN: 10600

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43621 AN: 67990

Other (OTH) AF: 0.696 AC: 1469 AN: 2112

Alfa AF: 0.669 Hom.: 19993

Bravo AF: 0.744

Asia WGS AF: 0.901 AC: 3131 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.54
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs7006733; hg19: chr8-11607990;