6-1611782-ACGGCGGCGGCGGCGG-ACGGCGGCGG

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001453.3(FOXC1):c.1356_1361delCGGCGG(p.Gly453_Gly454del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000451 in 1,440,534 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

FOXC1
NM_001453.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.10

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: Labcorp Genetics (formerly Invitae), G2P
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-ACGGCGG-A is Benign according to our data. Variant chr6-1611782-ACGGCGG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1624657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000465 (603/1297418) while in subpopulation AMR AF = 0.0013 (31/23816). AF 95% confidence interval is 0.000942. There are 1 homozygotes in GnomAdExome4. There are 287 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High AC in GnomAd4 at 47 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC1	NM_001453.3	MANE Select	c.1356_1361delCGGCGG	p.Gly453_Gly454del	disruptive_inframe_deletion	Exon 1 of 1	NP_001444.2	W6CJ52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC1	ENST00000645831.2	MANE Select	c.1356_1361delCGGCGG	p.Gly453_Gly454del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000493906.1	Q12948

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

143038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000311

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000341

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000423

Gnomad SAS

AF:

0.000676

Gnomad FIN

AF:

0.000214

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000339

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000787

AC:

AN:

64810

AF XY:

0.000637

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000903

Gnomad FIN exome

AF:

0.000449

Gnomad NFE exome

AF:

0.000521

Gnomad OTH exome

AF:

0.00420

GnomAD4 exome

AF:

0.000465

AC:

603

AN:

1297418

Hom.:

AF XY:

0.000449

AC XY:

287

AN XY:

639794

show subpopulations

African (AFR)

AF:

0.000232

AC:

AN:

25844

American (AMR)

AF:

0.00130

AC:

AN:

23816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22546

East Asian (EAS)

AF:

0.000565

AC:

AN:

28298

South Asian (SAS)

AF:

0.000953

AC:

AN:

69282

European-Finnish (FIN)

AF:

0.000271

AC:

AN:

33242

Middle Eastern (MID)

AF:

0.000209

AC:

AN:

4778

European-Non Finnish (NFE)

AF:

0.000431

AC:

446

AN:

1035988

Other (OTH)

AF:

0.000522

AC:

AN:

53624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000328

AC:

AN:

143116

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

AN XY:

69632

show subpopulations

African (AFR)

AF:

0.000336

AC:

AN:

38712

American (AMR)

AF:

0.000341

AC:

AN:

14668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3340

East Asian (EAS)

AF:

0.000424

AC:

AN:

4712

South Asian (SAS)

AF:

0.000676

AC:

AN:

4438

European-Finnish (FIN)

AF:

0.000214

AC:

AN:

9360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.000339

AC:

AN:

64808

Other (OTH)

AF:

0.00

AC:

AN:

1982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Axenfeld-Rieger syndrome type 3 (1)

FOXC1-related disorder (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.1

Mutation Taster

=177/23

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over