6-1613294-A-T

Variant names:

• chr6-1613294-A-T
• rs984253
• NM_001453.3:c.*1187A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001453.3(FOXC1):​c.*1187A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 230,834 control chromosomes in the GnomAD database, including 56,423 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (40216 hom., cov: 33)
  • Exomes 𝑓: 0.63 (16207 hom.)
• Consequence: FOXC1 NM_001453.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• anterior segment dysgenesis 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• Axenfeld-Rieger syndrome type 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• aniridia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• Axenfeld anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Axenfeld-Rieger syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated aniridia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Peters anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Rieger anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXC1	NM_001453.3	c.*1187A>T		3_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	ENST00000645831.2	c.*1187A>T		3_prime_UTR_variant	Exon 1 of 1		NM_001453.3	ENSP00000493906.1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107925 AN: 152026 Hom.: 40160 Cov.: 33

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.706

GnomAD4 exome AF: 0.629 AC: 49483 AN: 78690 Hom.: 16207 Cov.: 0 AF XY: 0.622 AC XY: 22751 AN XY: 36564

African (AFR) AF: 0.924 AC: 2693 AN: 2916

American (AMR) AF: 0.690 AC: 1261 AN: 1828

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2764 AN: 4086

East Asian (EAS) AF: 0.844 AC: 7852 AN: 9306

South Asian (SAS) AF: 0.858 AC: 455 AN: 530

European-Finnish (FIN) AF: 0.475 AC: 6941 AN: 14618

Middle Eastern (MID) AF: 0.732 AC: 284 AN: 388

European-Non Finnish (NFE) AF: 0.595 AC: 23522 AN: 39500

Other (OTH) AF: 0.673 AC: 3711 AN: 5518

GnomAD4 genome AF: 0.710 AC: 108032 AN: 152144 Hom.: 40216 Cov.: 33 AF XY: 0.710 AC XY: 52810 AN XY: 74384

African (AFR) AF: 0.926 AC: 38465 AN: 41524

American (AMR) AF: 0.699 AC: 10686 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2304 AN: 3470

East Asian (EAS) AF: 0.877 AC: 4546 AN: 5184

South Asian (SAS) AF: 0.852 AC: 4110 AN: 4824

European-Finnish (FIN) AF: 0.476 AC: 5030 AN: 10564

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40630 AN: 67980

Other (OTH) AF: 0.709 AC: 1499 AN: 2114

Alfa AF: 0.393 Hom.: 707

Bravo AF: 0.732

Asia WGS AF: 0.859 AC: 2988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.82
PhyloP100		0.052
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs984253; hg19: chr6-1613529;