6-1611567-G-GGGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001453.3(FOXC1):c.1139_1141dupGCG(p.Gly380dup) variant causes a disruptive 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 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.420

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

anterior segment dysgenesis 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
Axenfeld-Rieger syndrome type 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
aniridia
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
Axenfeld anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Axenfeld-Rieger syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
isolated aniridia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Peters anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Rieger anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FOXC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 6-1611567-G-GGGC is Benign according to our data. Variant chr6-1611567-G-GGGC is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001453.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC1	NM_001453.3	MANE Select	c.1139_1141dupGCG	p.Gly380dup	disruptive_inframe_insertion	Exon 1 of 1	NP_001444.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC1	ENST00000645831.2	MANE Select	c.1139_1141dupGCG	p.Gly380dup	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000493906.1

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

GnomAD2 exomes

AF:

0.0483

AC:

655

AN:

13566

AF XY:

0.0519

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 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

African (AFR)

AF:

0.0954

AC:

1886

AN:

19776

American (AMR)

AF:

0.206

AC:

1188

AN:

5756

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

1765

AN:

11234

East Asian (EAS)

AF:

0.538

AC:

5955

AN:

11066

South Asian (SAS)

AF:

0.271

AC:

6124

AN:

22606

European-Finnish (FIN)

AF:

0.141

AC:

2123

AN:

15018

Middle Eastern (MID)

AF:

0.197

AC:

480

AN:

2436

European-Non Finnish (NFE)

AF:

0.199

AC:

173061

AN:

868856

Other (OTH)

AF:

0.210

AC:

7726

AN:

36704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

8652

17305

25957

34610

43262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7838

15676

23514

31352

39190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.223

AC:

32661

AN:

146464

Hom.:

4474

Cov.:

AF XY:

0.232

AC XY:

16535

AN XY:

71288

show subpopulations

African (AFR)

AF:

0.120

AC:

4903

AN:

40854

American (AMR)

AF:

0.296

AC:

4373

AN:

14756

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

844

AN:

3386

East Asian (EAS)

AF:

0.668

AC:

3230

AN:

4834

South Asian (SAS)

AF:

0.357

AC:

1711

AN:

4790

European-Finnish (FIN)

AF:

0.254

AC:

2210

AN:

8690

Middle Eastern (MID)

AF:

0.214

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.221

AC:

14594

AN:

65926

Other (OTH)

AF:

0.224

AC:

456

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1189

2378

3568

4757

5946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.0802

Hom.:

107

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 09, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Aug 02, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Axenfeld-Rieger syndrome type 3

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.42

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over