chr6-1610202-C-T
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 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
NM_001453.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.740
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]
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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 GnomAd at 1978 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXC1 | NM_001453.3 | c.-244C>T | 5_prime_UTR_variant | 1/1 | ENST00000645831.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXC1 | ENST00000645831.2 | c.-244C>T | 5_prime_UTR_variant | 1/1 | NM_001453.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0130 AC: 1978AN: 151612Hom.: 33 Cov.: 31
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GnomAD4 genome ? AF: 0.0130 AC: 1976AN: 151720Hom.: 33 Cov.: 31 AF XY: 0.0132 AC XY: 981AN XY: 74168
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ClinVar
Significance: Likely benign
Submissions summary: Pathogenic:1Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1Benign:1
Pathogenic, no assertion criteria provided | not provided | Human Genetics School of Medicine of Albacete, Castilla-La Mancha University | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 24, 2021 | See Variant Classification Assertion Criteria. - |
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
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at