Variant 6-1611782-ACGGCGGCGGCGG-ACGGCGGCGG 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.1359_1361delCGG(p.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 0.00269 in 1,402,412 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 19)

Exomes 𝑓: 0.0027 ( 3 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: 0.744

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-ACGG-A is Benign according to our data. Variant chr6-1611782-ACGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 193212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0027 (386/143064) while in subpopulation AFR AF= 0.00891 (345/38706). AF 95% confidence interval is 0.00814. There are 1 homozygotes in gnomad4. There are 197 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.

BS2

High AC in GnomAd4 at 386 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXC1	NM_001453.3 linkuse as main transcript	c.1359_1361delCGG	p.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.1359_1361delCGG	p.Gly454del	disruptive_inframe_deletion	1/1		NM_001453.3	ENSP00000493906.1		Q12948

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

379

AN:

142986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00875

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000450

Gnomad FIN

AF:

0.000536

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000339

Gnomad OTH

AF:

0.00255

GnomAD3 exomes

AF:

0.0159

AC:

1032

AN:

64810

Hom.:

AF XY:

0.0149

AC XY:

560

AN XY:

37658

show subpopulations

Gnomad AFR exome

AF:

0.0155

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.0298

Gnomad SAS exome

AF:

0.0144

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.00268

AC:

3380

AN:

1259348

Hom.:

AF XY:

0.00298

AC XY:

1847

AN XY:

619338

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.00881

Gnomad4 ASJ exome

AF:

0.00472

Gnomad4 EAS exome

AF:

0.00254

Gnomad4 SAS exome

AF:

0.00918

Gnomad4 FIN exome

AF:

0.00431

Gnomad4 NFE exome

AF:

0.00180

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.00270

AC:

386

AN:

143064

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

197

AN XY:

69604

show subpopulations

Gnomad4 AFR

AF:

0.00891

Gnomad4 AMR

AF:

0.000477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000451

Gnomad4 FIN

AF:

0.000536

Gnomad4 NFE

AF:

0.000340

Gnomad4 OTH

AF:

0.00253

ClinVar

Significance: Benign/Likely 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)

Mar 15, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 20, 2021

See Variant Classification Assertion Criteria. -

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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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