Genetic Variant FOXC1:c.-419_-417dupCCC (chr6-1610015-G-GCCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001453.3(FOXC1):c.-419_-417dupCCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.036 ( 21 hom., cov: 13)

Exomes 𝑓: 0.0078 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXC1
NM_001453.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.-419_-417dupCCC		5_prime_UTR	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.-419_-417dupCCC		5_prime_UTR	Exon 1 of 1	ENSP00000493906.1	Q12948

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

3303

AN:

92552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0366

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.0393

Gnomad EAS

AF:

0.0185

Gnomad SAS

AF:

0.0173

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0416

Gnomad OTH

AF:

0.0329

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00781

AC:

AN:

128

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00909

AC:

AN:

110

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0357

AC:

3304

AN:

92546

Hom.:

Cov.:

AF XY:

0.0340

AC XY:

1474

AN XY:

43394

show subpopulations

African (AFR)

AF:

0.0365

AC:

785

AN:

21490

American (AMR)

AF:

0.0258

AC:

231

AN:

8948

Ashkenazi Jewish (ASJ)

AF:

0.0393

AC:

107

AN:

2724

East Asian (EAS)

AF:

0.0185

AC:

AN:

3506

South Asian (SAS)

AF:

0.0174

AC:

AN:

2522

European-Finnish (FIN)

AF:

0.0147

AC:

AN:

4434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

166

European-Non Finnish (NFE)

AF:

0.0417

AC:

1955

AN:

46934

Other (OTH)

AF:

0.0327

AC:

AN:

1286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

136

272

409

545

681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

6-1610015-GCCCCC-GCCCCCCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over