chr2-38074520-CG-C
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000104.4(CYP1B1):c.868delC(p.Arg290AlafsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CYP1B1
NM_000104.4 frameshift
NM_000104.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.35
Publications
7 publications found
Genes affected
CYP1B1 (HGNC:2597): (cytochrome P450 family 1 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The enzyme encoded by this gene localizes to the endoplasmic reticulum and metabolizes procarcinogens such as polycyclic aromatic hydrocarbons and 17beta-estradiol. Mutations in this gene have been associated with primary congenital glaucoma; therefore it is thought that the enzyme also metabolizes a signaling molecule involved in eye development, possibly a steroid. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-38074520-CG-C is Pathogenic according to our data. Variant chr2-38074520-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 2681137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000104.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CYP1B1 | TSL:1 MANE Select | c.868delC | p.Arg290AlafsTer3 | frameshift | Exon 2 of 3 | ENSP00000478561.1 | Q16678 | ||
| CYP1B1 | TSL:4 | c.868delC | p.Arg290AlafsTer3 | frameshift | Exon 2 of 3 | ENSP00000478839.2 | Q16678 | ||
| CYP1B1 | TSL:5 | c.868delC | p.Arg290AlafsTer3 | frameshift | Exon 2 of 3 | ENSP00000483678.1 | Q16678 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1456096Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 723912
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1456096
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
723912
African (AFR)
AF:
AC:
0
AN:
33434
American (AMR)
AF:
AC:
0
AN:
43626
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25962
East Asian (EAS)
AF:
AC:
0
AN:
39482
South Asian (SAS)
AF:
AC:
0
AN:
85454
European-Finnish (FIN)
AF:
AC:
0
AN:
52588
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1109638
Other (OTH)
AF:
AC:
0
AN:
60154
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
Anterior segment dysgenesis 6 (1)
1
-
-
Congenital glaucoma (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.