6-1611782-ACGGCGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGG

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.1359_1361dupCGG(p.Gly454dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,439,242 control chromosomes in the GnomAD database, including 27,814 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G454G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.28 ( 5705 hom., cov: 19)

Exomes 𝑓: 0.23 ( 22109 hom. )

Consequence

FOXC1
NM_001453.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.613

Publications

15 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 6-1611782-A-ACGG is Benign according to our data. Variant chr6-1611782-A-ACGG is described in ClinVar as Benign. ClinVar VariationId is 93747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXC1	NM_001453.3 link	c.1359_1361dupCGG	p.Gly454dup	disruptive_inframe_insertion	Exon 1 of 1	ENST00000645831.2	NP_001444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXC1	ENST00000645831.2 link	c.1359_1361dupCGG	p.Gly454dup	disruptive_inframe_insertion	Exon 1 of 1		NM_001453.3	ENSP00000493906.1		Q12948

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

40439

AN:

142866

Hom.:

5695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.275

GnomAD2 exomes

AF:

0.240

AC:

15558

AN:

64810

AF XY:

0.235

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.337

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.315

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.233

AC:

301476

AN:

1296298

Hom.:

22109

Cov.:

AF XY:

0.231

AC XY:

147705

AN XY:

639150

show subpopulations

African (AFR)

AF:

0.284

AC:

7341

AN:

25830

American (AMR)

AF:

0.306

AC:

7257

AN:

23736

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

4411

AN:

22490

East Asian (EAS)

AF:

0.367

AC:

10369

AN:

28230

South Asian (SAS)

AF:

0.245

AC:

16906

AN:

68982

European-Finnish (FIN)

AF:

0.197

AC:

6542

AN:

33200

Middle Eastern (MID)

AF:

0.184

AC:

876

AN:

4772

European-Non Finnish (NFE)

AF:

0.227

AC:

234659

AN:

1035480

Other (OTH)

AF:

0.245

AC:

13115

AN:

53578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

13981

27962

41943

55924

69905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9002

18004

27006

36008

45010

<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:

0.283

AC:

40485

AN:

142944

Hom.:

5705

Cov.:

AF XY:

0.284

AC XY:

19767

AN XY:

69530

show subpopulations

African (AFR)

AF:

0.327

AC:

12659

AN:

38666

American (AMR)

AF:

0.338

AC:

4949

AN:

14646

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

727

AN:

3336

East Asian (EAS)

AF:

0.415

AC:

1952

AN:

4706

South Asian (SAS)

AF:

0.333

AC:

1475

AN:

4436

European-Finnish (FIN)

AF:

0.225

AC:

2103

AN:

9340

Middle Eastern (MID)

AF:

0.169

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.245

AC:

15886

AN:

64736

Other (OTH)

AF:

0.276

AC:

547

AN:

1982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1389

2777

4166

5554

6943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.0839

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

May 09, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Axenfeld-Rieger syndrome type 3

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Anterior segment dysgenesis 3

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.61

Mutation Taster

=93/7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over