Variant 6-1611567-GGGCGGCGGC-GGGCGGCGGCGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1BP6_Very_StrongBA1

The NM_001453.3(FOXC1):c.1139_1141dup(p.Gly380dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,139,916 control chromosomes in the GnomAD database, including 26,099 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4474 hom., cov: 24)

Exomes 𝑓: 0.20 ( 21625 hom. )

Consequence

FOXC1
NM_001453.3 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.420

Variant links:

Genes affected

FOXC1 (HGNC:3800): (forkhead box C1) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it has been shown to play a role in the regulation of embryonic and ocular development. Mutations in this gene cause various glaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, and Axenfeld-Rieger anomaly. [provided by RefSeq, Jul 2008]

FOXC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_001453.3

BP6

Variant 6-1611567-G-GGGC is Benign according to our data. Variant chr6-1611567-G-GGGC is described in ClinVar as [Benign]. Clinvar id is 193213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXC1	NM_001453.3 linkuse as main transcript	c.1139_1141dup	p.Gly380dup	inframe_insertion	1/1	ENST00000645831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXC1	ENST00000645831.2 linkuse as main transcript	c.1139_1141dup	p.Gly380dup	inframe_insertion	1/1		NM_001453.3	P1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

32657

AN:

146364

Hom.:

4481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.0483

AC:

655

AN:

13566

Hom.:

AF XY:

0.0519

AC XY:

461

AN XY:

8876

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.0509

Gnomad ASJ exome

AF:

0.0405

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.0626

Gnomad FIN exome

AF:

0.0538

Gnomad NFE exome

AF:

0.0420

Gnomad OTH exome

AF:

0.0391

GnomAD4 exome

AF:

0.202

AC:

200308

AN:

993452

Hom.:

21625

Cov.:

AF XY:

0.199

AC XY:

94319

AN XY:

474342

show subpopulations

Gnomad4 AFR exome

AF:

0.0954

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.538

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.210

GnomAD4 genome

AF:

0.223

AC:

32661

AN:

146464

Hom.:

4474

Cov.:

AF XY:

0.232

AC XY:

16535

AN XY:

71288

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.296

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.668

Gnomad4 SAS

AF:

0.357

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.221

Gnomad4 OTH

AF:

0.224

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 09, 2014	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 02, 2018

- -

Axenfeld-Rieger syndrome type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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