chr2-38075070-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000104.4(CYP1B1):āc.319C>Gā(p.Leu107Val) variant causes a missense change. The variant allele was found at a frequency of 0.0001 in 1,583,766 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000104.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP1B1 | NM_000104.4 | c.319C>G | p.Leu107Val | missense_variant | Exon 2 of 3 | ENST00000610745.5 | NP_000095.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152248Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000341 AC: 67AN: 196756Hom.: 0 AF XY: 0.000311 AC XY: 34AN XY: 109400
GnomAD4 exome AF: 0.0000985 AC: 141AN: 1431400Hom.: 0 Cov.: 35 AF XY: 0.0000985 AC XY: 70AN XY: 710964
GnomAD4 genome AF: 0.000118 AC: 18AN: 152366Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11AN XY: 74510
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: CYP1B1 c.319C>G (p.Leu107Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00034 in 196756 control chromosomes, predominantly at a frequency of 0.0042 within the East Asian subpopulation in the gnomAD database. This frequency similar to the expected for a pathogenic variant in CYP1B1 causing Primary Congenital Glaucoma (0.00034 vs 0.0043), suggesting the variant might be a polymorphism found in the East Asian population. c.319C>G has been reported in the literature in individuals affected with Primary Congenital Glaucoma without strong evidence for causality, as well as in controls and unaffected individuals (eg. Chen_2008, Kim_2011, Chen_2014, Chen_2015, Gong_2015, Qiao_2021). These reports do not provide unequivocal conclusions about association of the variant with Primary Congenital Glaucoma. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Three submitters classified the variant as VUS while one classified as benign. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Irido-corneo-trabecular dysgenesis Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Glaucoma 3A Uncertain:1
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Congenital glaucoma Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at