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GeneBe

rs10012

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2_SupportingPM5BP4_Moderate

The NM_000104.4(CYP1B1):c.142C>T(p.Arg48Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152100 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign 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. R48G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

CYP1B1
NM_000104.4 missense

Scores

2
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.744

Links

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.00000657 (1/152100) . There are 0 homozygotes in gnomad. There are 1 alleles in male gnomad subpopulation. Median coverage is 34. This position pass quality control queck.
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr2-38075247-G-C is described in Lovd as [Pathogenic].
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11410883).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP1B1NM_000104.4 linkuse as main transcriptc.142C>T p.Arg48Trp missense_variant 2/3 ENST00000610745.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP1B1ENST00000610745.5 linkuse as main transcriptc.142C>T p.Arg48Trp missense_variant 2/31 NM_000104.4 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152100
Hom.:
0
Cov.:
34
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:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.94e-7
AC:
1
AN:
1441286
Hom.:
0
AF XY:
0.00000140
AC XY:
1
AN XY:
715982
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:
9.04e-7
Gnomad4 OTH exome
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.69
Cadd
Benign
17
Dann
Benign
0.92
DEOGEN2
Benign
0.13
T;T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.030
N
M_CAP
Uncertain
0.27
D
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.55
N;N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.49
T
Sift4G
Benign
0.091
T;T;.
Vest4
0.13
MVP
0.19
ClinPred
0.96
D
GERP RS
-4.8
Varity_R
0.065
gMVP
0.61

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: rs10012; hg19: chr2-38302390;