Variant chr6-1611782-ACGGCGG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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:3

Conservation

PhyloP100: 3.10

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-ACGGCGG-A is Benign according to our data. Variant chr6-1611782-ACGGCGG-A is described in ClinVar as [Likely_benign]. Clinvar id 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. gnomad4_exome 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 gnomad4_exome. There are 287 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXC1	NM_001453.3 linkuse as main transcript	c.1356_1361delCGGCGG	p.Gly453_Gly454del	disruptive_inframe_deletion	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.1356_1361delCGGCGG	p.Gly453_Gly454del	disruptive_inframe_deletion	1/1		NM_001453.3	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

GnomAD3 exomes

AF:

0.000787

AC:

AN:

64810

Hom.:

AF XY:

0.000637

AC XY:

AN XY:

37658

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 SAS exome

AF:

0.000810

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

Gnomad4 AFR exome

AF:

0.000232

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000565

Gnomad4 SAS exome

AF:

0.000953

Gnomad4 FIN exome

AF:

0.000271

Gnomad4 NFE exome

AF:

0.000431

Gnomad4 OTH exome

AF:

0.000522

GnomAD4 genome

AF:

0.000328

AC:

AN:

143116

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

AN XY:

69632

show subpopulations

Gnomad4 AFR

AF:

0.000336

Gnomad4 AMR

AF:

0.000341

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000424

Gnomad4 SAS

AF:

0.000676

Gnomad4 FIN

AF:

0.000214

Gnomad4 NFE

AF:

0.000339

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

FOXC1: BS1, BS2 -

Axenfeld-Rieger syndrome type 3

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2023

- -

FOXC1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 19, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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