Genetic Variant CYP1B1:p.Pro52Arg (chr2-38075234-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PP2PP3_Moderate

The NM_000104.4(CYP1B1):c.155C>G(p.Pro52Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000696 in 1,436,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P52L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

CYP1B1
NM_000104.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.53

Publications

0 publications found

Variant links:

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]

CYP1B1 links:

CYP1B1-AS1 (HGNC:28543): (CYP1B1 antisense RNA 1)

CYP1B1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 35 curated pathogenic missense variants (we use a threshold of 10). The gene has 9 curated benign missense variants. Trascript score misZ: -2.0997 (below the threshold of 3.09). GenCC associations: The gene is linked to Peters anomaly, anterior segment dysgenesis 6, glaucoma 3A, CYP1B1-related glaucoma with or without anterior segment dysgenesis, congenital glaucoma.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4 link	c.155C>G	p.Pro52Arg	missense_variant	Exon 2 of 3	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5 link	c.155C>G	p.Pro52Arg	missense_variant	Exon 2 of 3	1	NM_000104.4	ENSP00000478561.1		Q16678

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000696

AC:

AN:

1436896

Hom.:

Cov.:

AF XY:

0.00000701

AC XY:

AN XY:

713554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33304

American (AMR)

AF:

0.00

AC:

AN:

41964

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25696

East Asian (EAS)

AF:

0.00

AC:

AN:

39088

South Asian (SAS)

AF:

0.00

AC:

AN:

84254

European-Finnish (FIN)

AF:

0.0000235

AC:

AN:

42638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4970

European-Non Finnish (NFE)

AF:

0.00000724

AC:

AN:

1105320

Other (OTH)

AF:

0.0000168

AC:

AN:

59662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

D;D;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Pathogenic

0.97

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.6

H;H;.

PhyloP100

5.5

PrimateAI

Uncertain

0.68

Sift4G

Pathogenic

0.0

D;D;.

Vest4

0.58

MVP

0.51

ClinPred

0.98

GERP RS

4.4

Varity_R

0.39

gMVP

0.88

Mutation Taster

=9/91

disease causing

(source)

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over