rs13273672

Variant names:

• chr8-11754872-T-C
• rs13273672
• NM_001308093.3:c.913-174T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-11754872-T-C
• chr8-11754872-T-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.913-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,066 control chromosomes in the GnomAD database, including 9,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (9551 hom., cov: 32)
• Consequence: GATA4 NM_001308093.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53
• Publications: 33 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=-0.91).
• BP6: Variant 8-11754872-T-C is Benign according to our data. Variant chr8-11754872-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA4	NM_001308093.3	MANE Select	c.913-174T>C		intron	N/A	NP_001295022.1	P43694-2
	GATA4	NM_002052.5		c.910-174T>C		intron	N/A	NP_002043.2
	GATA4	NM_001308094.2		c.292-174T>C		intron	N/A	NP_001295023.1	B3KUF4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA4	ENST00000532059.6	TSL:1 MANE Select	c.913-174T>C		intron	N/A	ENSP00000435712.1	P43694-2
	GATA4	ENST00000886854.1		c.931-174T>C		intron	N/A	ENSP00000556913.1
	GATA4	ENST00000886846.1		c.913-174T>C		intron	N/A	ENSP00000556905.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52868 AN: 151946 Hom.: 9558 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.348 AC: 52887 AN: 152066 Hom.: 9551 Cov.: 32 AF XY: 0.355 AC XY: 26403 AN XY: 74308

African (AFR) AF: 0.355 AC: 14738 AN: 41466

American (AMR) AF: 0.367 AC: 5614 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3466

East Asian (EAS) AF: 0.602 AC: 3114 AN: 5172

South Asian (SAS) AF: 0.379 AC: 1828 AN: 4824

European-Finnish (FIN) AF: 0.421 AC: 4437 AN: 10548

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21265 AN: 67990

Other (OTH) AF: 0.333 AC: 703 AN: 2114

Alfa AF: 0.327 Hom.: 27235

Bravo AF: 0.347

Asia WGS AF: 0.472 AC: 1637 AN: 3478

ClinVar

ClinVar submissions

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	-0.91
CADD	Benign	0.24
DANN	Benign	0.25
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: rs13273672; hg19: chr8-11612381;