Variant chr6-1610202-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001453.3(FOXC1):c.-244C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 152,226 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.013 ( 33 hom., cov: 31)

Exomes 𝑓: 0.0059 ( 0 hom. )

Consequence

FOXC1
NM_001453.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter P:1B:2

Conservation

PhyloP100: -0.740

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-1610202-C-T is Benign according to our data. Variant chr6-1610202-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 183250.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.013 (1976/151720) while in subpopulation NFE AF= 0.0208 (1409/67820). AF 95% confidence interval is 0.0199. There are 33 homozygotes in gnomad4. There are 981 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1976 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXC1	NM_001453.3 link	c.-244C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 1	ENST00000645831.2	NP_001444.2
FOXC1	NM_001453.3 link	c.-244C>T		5_prime_UTR_variant	Exon 1 of 1	ENST00000645831.2	NP_001444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXC1	ENST00000645831 link	c.-244C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 1		NM_001453.3	ENSP00000493906.1		Q12948
FOXC1	ENST00000645831 link	c.-244C>T		5_prime_UTR_variant	Exon 1 of 1		NM_001453.3	ENSP00000493906.1		Q12948

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1978

AN:

151612

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00715

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0310

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0208

Gnomad OTH

AF:

0.00337

GnomAD4 exome

AF:

0.00593

AC:

AN:

506

Hom.:

Cov.:

AF XY:

0.00806

AC XY:

AN XY:

248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00620

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0130

AC:

1976

AN:

151720

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

981

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.00714

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0310

Gnomad4 NFE

AF:

0.0208

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.0238

Hom.:

Bravo

AF:

0.00931

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 24, 2021	See Variant Classification Assertion Criteria. -
Pathogenic, no assertion criteria provided	not provided	Human Genetics School of Medicine of Albacete, Castilla-La Mancha University	-	- -

Anterior segment dysgenesis 3

Benign:1

Benign, no assertion criteria provided

curation

Reproductive Health Research and Development, BGI Genomics

Jan 06, 2020

NG_009368.1(NM_001453.2):c.-244C>T in FOXC1 gene has an allele frequency of 0.041 in European (non-Finnish) subpopulation in the gnomAD database, including 27 homozygous occurrences. Taken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1, BS2. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.1

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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