Variant 6-1611782-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
FOXC1	NM_001453.3 linkuse as main transcript	c.1359_1361dupCGG	p.Gly454dup	disruptive_inframe_insertion	1/1	ENST00000645831.2	NP_001444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXC1	ENST00000645831.2 linkuse as main transcript	c.1359_1361dupCGG	p.Gly454dup	disruptive_inframe_insertion	1/1		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

GnomAD3 exomes

AF:

0.240

AC:

15558

AN:

64810

Hom.:

826

AF XY:

0.235

AC XY:

8867

AN XY:

37658

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 SAS exome

AF:

0.242

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

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.306

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.367

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.283

AC:

40485

AN:

142944

Hom.:

5705

Cov.:

AF XY:

0.284

AC XY:

19767

AN XY:

69530

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.245

Gnomad4 OTH

AF:

0.276

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2014	- -

Axenfeld-Rieger syndrome type 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

Anterior segment dysgenesis 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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