rs104893628

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_000104.4(CYP1B1):ā€‹c.694G>Cā€‹(p.Gly232Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

CYP1B1
NM_000104.4 missense

Scores

7
8
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.01
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.913
PP5
Variant 2-38074695-C-G is Pathogenic according to our data. Variant chr2-38074695-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 7740.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-38074695-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP1B1NM_000104.4 linkuse as main transcriptc.694G>C p.Gly232Arg missense_variant 2/3 ENST00000610745.5 NP_000095.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP1B1ENST00000610745.5 linkuse as main transcriptc.694G>C p.Gly232Arg missense_variant 2/31 NM_000104.4 ENSP00000478561.1 Q16678

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152272
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1460134
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726314
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152272
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Glaucoma 3A Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMSep 01, 2004- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.49
T;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Pathogenic
0.98
.;D
M_CAP
Pathogenic
0.66
D
MetaRNN
Pathogenic
0.91
D;D
MetaSVM
Uncertain
0.17
D
MutationAssessor
Uncertain
2.4
M;M
PrimateAI
Uncertain
0.64
T
Sift4G
Uncertain
0.022
D;D
Vest4
0.93
MVP
0.44
ClinPred
0.94
D
GERP RS
4.7
Varity_R
0.89
gMVP
0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs104893628; hg19: chr2-38301838; API