Variant 6-1610850-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001453.3(FOXC1):c.405C>T(p.Cys135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,614,076 control chromosomes in the GnomAD database, including 384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 187 hom., cov: 31)

Exomes 𝑓: 0.0035 ( 197 hom. )

Consequence

FOXC1
NM_001453.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.75

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 6-1610850-C-T is Benign according to our data. Variant chr6-1610850-C-T is described in ClinVar as [Benign]. Clinvar id is 167085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0946 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.405C>T	p.Cys135=	synonymous_variant	1/1	ENST00000645831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXC1	ENST00000645831.2 linkuse as main transcript	c.405C>T	p.Cys135=	synonymous_variant	1/1		NM_001453.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0285

AC:

4336

AN:

152092

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000912

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.00793

AC:

1993

AN:

251402

Hom.:

AF XY:

0.00583

AC XY:

792

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.00549

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000871

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00349

AC:

5096

AN:

1461868

Hom.:

197

Cov.:

AF XY:

0.00309

AC XY:

2246

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.00613

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000893

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000607

Gnomad4 OTH exome

AF:

0.00724

GnomAD4 genome

AF:

0.0286

AC:

4353

AN:

152208

Hom.:

187

Cov.:

AF XY:

0.0269

AC XY:

2004

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0971

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.0325

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 28, 2014

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Axenfeld-Rieger syndrome type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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