rs200040370
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001453.3(FOXC1):c.216G>A(p.Gln72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
FOXC1
NM_001453.3 synonymous
NM_001453.3 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 2.81
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 6-1610661-G-A is Benign according to our data. Variant chr6-1610661-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 469650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.81 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00021 (32/152162) while in subpopulation AMR AF= 0.00098 (15/15300). AF 95% confidence interval is 0.000604. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 32 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXC1 | NM_001453.3 | c.216G>A | p.Gln72= | synonymous_variant | 1/1 | ENST00000645831.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXC1 | ENST00000645831.2 | c.216G>A | p.Gln72= | synonymous_variant | 1/1 | NM_001453.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152046Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000279 AC: 70AN: 250696Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135804
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GnomAD4 exome AF: 0.000121 AC: 177AN: 1461294Hom.: 0 Cov.: 32 AF XY: 0.000116 AC XY: 84AN XY: 726960
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GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152162Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16AN XY: 74370
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Axenfeld-Rieger syndrome type 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
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