6-1610015-GCCC-GCCCC

Variant names:

• chr6-1610015-G-GC
• rs562673925
• NM_001453.3:c.-417dupC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001453.3(FOXC1):​c.-417dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0027 (9 hom., cov: 13)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXC1 NM_001453.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0027 (250/92558) while in subpopulation AFR AF= 0.00493 (106/21484). AF 95% confidence interval is 0.00417. There are 9 homozygotes in gnomad4. There are 123 alleles in male gnomad4 subpopulation. Median coverage is 13. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 250 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXC1	NM_001453.3	c.-417dupC		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	c.-417dupC		5_prime_UTR_variant	Exon 1 of 1		NM_001453.3	ENSP00000493906.1

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 248 AN: 92564 Hom.: 9 Cov.: 13

Gnomad AFR AF: 0.00480

Gnomad AMI AF: 0.00560

Gnomad AMR AF: 0.00312

Gnomad ASJ AF: 0.00110

Gnomad EAS AF: 0.00455

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.000226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.00156

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 128 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 94

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00270 AC: 250 AN: 92558 Hom.: 9 Cov.: 13 AF XY: 0.00283 AC XY: 123 AN XY: 43406

Gnomad4 AFR AF: 0.00493

Gnomad4 AMR AF: 0.00312

Gnomad4 ASJ AF: 0.00110

Gnomad4 EAS AF: 0.00457

Gnomad4 SAS AF: 0.00357

Gnomad4 FIN AF: 0.000226

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.00156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs562673925; hg19: chr6-1610250;