chr8-11704309-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001308093.3(GATA4):c.-458+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 152,368 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 306 hom., cov: 33)

Exomes 𝑓: 0.040 ( 0 hom. )

Consequence

GATA4
NM_001308093.3 splice_region, intron

Scores

Splicing: ADA: 0.7050

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.27

Publications

7 publications found

Variant links:

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

GATA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 8-11704309-G-A is Benign according to our data. Variant chr8-11704309-G-A is described in ClinVar as Benign. ClinVar VariationId is 1301633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA4	NM_001308093.3	MANE Select	c.-458+5G>A	splice_region intron	N/A	NP_001295022.1	P43694-2
GATA4	NM_002052.5		c.-458+5G>A	splice_region intron	N/A	NP_002043.2
GATA4	NM_001308094.2		c.-6+3531G>A	intron	N/A	NP_001295023.1	B3KUF4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA4	ENST00000532059.6	TSL:1 MANE Select	c.-458+5G>A	splice_region intron	N/A	ENSP00000435712.1	P43694-2
GATA4	ENST00000532977.1	TSL:1	c.-458+3531G>A	intron	N/A	ENSP00000473671.1	B6DU75
GATA4	ENST00000886854.1		c.-458+5G>A	splice_region intron	N/A	ENSP00000556913.1

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8106

AN:

152200

Hom.:

308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0643

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0811

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0737

Gnomad OTH

AF:

0.0598

GnomAD4 exome

AF:

0.0400

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0278

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0333

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0532

AC:

8096

AN:

152318

Hom.:

306

Cov.:

AF XY:

0.0530

AC XY:

3948

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0139

AC:

578

AN:

41594

American (AMR)

AF:

0.0405

AC:

620

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0643

AC:

223

AN:

3470

East Asian (EAS)

AF:

0.000966

AC:

AN:

5174

South Asian (SAS)

AF:

0.118

AC:

571

AN:

4828

European-Finnish (FIN)

AF:

0.0811

AC:

861

AN:

10618

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0737

AC:

5011

AN:

68006

Other (OTH)

AF:

0.0591

AC:

125

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

378

756

1133

1511

1889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0290

Hom.:

Bravo

AF:

0.0476

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

2.3

PromoterAI

-0.23

Neutral

(source)

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.71

dbscSNV1_RF

Benign

0.63

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over