rs398123612

Positions:

• chr6-1611782-ACGGCGGCGGCGG-A
• chr6-1611782-ACGGCGGCGGCGG-ACGG
• chr6-1611782-ACGGCGGCGGCGG-ACGGCGG
• chr6-1611782-ACGGCGGCGGCGG-ACGGCGGCGG
• chr6-1611782-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGG
• chr6-1611782-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGG
• chr6-1611782-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGG
• chr6-1611782-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGG
• chr6-1611782-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGGCGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001453.3(FOXC1):​c.1350_1361delCGGCGGCGGCGG​(p.Gly451_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 0.0000257 in 1,440,688 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: FOXC1 NM_001453.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXC1	NM_001453.3	c.1350_1361delCGGCGGCGGCGG	p.Gly451_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	c.1350_1361delCGGCGGCGGCGG	p.Gly451_Gly454del	disruptive_inframe_deletion	1/1		NM_001453.3	ENSP00000493906.1

Frequencies

GnomAD3 genomes AF: 0.0000350 AC: 5 AN: 143040 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000463

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000247 AC: 32 AN: 1297648 Hom.: 0 AF XY: 0.0000188 AC XY: 12 AN XY: 639910

Gnomad4 AFR exome AF: 0.0000387

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000353

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.0000559

GnomAD4 genome AF: 0.0000350 AC: 5 AN: 143040 Hom.: 0 Cov.: 19 AF XY: 0.0000144 AC XY: 1 AN XY: 69544

Gnomad4 AFR AF: 0.0000518

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000463

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs398123612; hg19: chr6-1612017;