Variant 8-11704309-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1301633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11704309-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3 link	c.-458+5G>A		splice_region_variant, intron_variant	Intron 1 of 6	ENST00000532059.6	NP_001295022.1	P43694-2B3KUF4B6DU75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6 link	c.-458+5G>A		splice_region_variant, intron_variant	Intron 1 of 6	1	NM_001308093.3	ENSP00000435712.1		P43694-2

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0333

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0532

AC:

8096

AN:

152318

Hom.:

306

Cov.:

AF XY:

0.0530

AC XY:

3948

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.0405

Gnomad4 ASJ

AF:

0.0643

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0811

Gnomad4 NFE

AF:

0.0737

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0268

Hom.:

Bravo

AF:

0.0476

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 11, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over