chr6-1610015-GC-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001453.3(FOXC1):​c.-417delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (72 hom., cov: 13)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXC1 NM_001453.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 6-1610015-GC-G is Benign according to our data. Variant chr6-1610015-GC-G is described in ClinVar as Benign. ClinVar VariationId is 1220557.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001453.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC1	NM_001453.3	MANE Select	c.-417delC		5_prime_UTR	Exon 1 of 1	NP_001444.2	W6CJ52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXC1	ENST00000645831.2	MANE Select	c.-417delC		5_prime_UTR	Exon 1 of 1	ENSP00000493906.1	Q12948

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 5845 AN: 92366 Hom.: 72 Cov.: 13

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0168

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.0163

Gnomad NFE AF: 0.0585

Gnomad OTH AF: 0.0563

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 110

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0633 AC: 5851 AN: 92360 Hom.: 72 Cov.: 13 AF XY: 0.0613 AC XY: 2657 AN XY: 43320

African (AFR) AF: 0.104 AC: 2232 AN: 21430

American (AMR) AF: 0.0528 AC: 474 AN: 8972

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 47 AN: 2722

East Asian (EAS) AF: 0.0226 AC: 79 AN: 3496

South Asian (SAS) AF: 0.0421 AC: 106 AN: 2520

European-Finnish (FIN) AF: 0.0206 AC: 91 AN: 4426

Middle Eastern (MID) AF: 0.0181 AC: 3 AN: 166

European-Non Finnish (NFE) AF: 0.0585 AC: 2738 AN: 46804

Other (OTH) AF: 0.0559 AC: 72 AN: 1288

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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

Other links and lift over

dbSNP: rs562673925; hg19: chr6-1610250;