rs2645400

Variant names:

• chr8-11751907-T-G
• rs2645400
• NM_001308093.3:c.912+1671T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308093.3(GATA4):​c.912+1671T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,120 control chromosomes in the GnomAD database, including 6,897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6897 hom., cov: 32)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.912+1671T>G		intron_variant	Intron 4 of 6	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.912+1671T>G		intron_variant	Intron 4 of 6	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42234 AN: 152002 Hom.: 6896 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.278 AC: 42253 AN: 152120 Hom.: 6897 Cov.: 32 AF XY: 0.283 AC XY: 21025 AN XY: 74354

African (AFR) AF: 0.108 AC: 4472 AN: 41534

American (AMR) AF: 0.291 AC: 4446 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1252 AN: 3464

East Asian (EAS) AF: 0.303 AC: 1565 AN: 5170

South Asian (SAS) AF: 0.374 AC: 1802 AN: 4818

European-Finnish (FIN) AF: 0.414 AC: 4372 AN: 10556

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23489 AN: 67978

Other (OTH) AF: 0.284 AC: 601 AN: 2114

Alfa AF: 0.303 Hom.: 7831

Bravo AF: 0.259

Asia WGS AF: 0.356 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		-0.034
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: rs2645400; hg19: chr8-11609416;