chr15-74721222-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001319217.2(CYP1A1):c.1143C>G(p.Phe381Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
CYP1A1
NM_001319217.2 missense
NM_001319217.2 missense
Scores
4
6
9
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.34
Genes affected
CYP1A1 (HGNC:2595): (cytochrome P450 family 1 subfamily A member 1) This gene, CYP1A1, 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. This protein localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. The gene has been associated with lung cancer risk. A related family member, CYP1A2, is located approximately 25 kb away from CYP1A1 on chromosome 15. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP1A1 | NM_001319217.2 | c.1143C>G | p.Phe381Leu | missense_variant | 5/7 | ENST00000379727.8 | NP_001306146.1 | |
CYP1A1 | NM_000499.5 | c.1143C>G | p.Phe381Leu | missense_variant | 5/7 | NP_000490.1 | ||
CYP1A1 | NM_001319216.2 | c.1143C>G | p.Phe381Leu | missense_variant | 5/6 | NP_001306145.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP1A1 | ENST00000379727.8 | c.1143C>G | p.Phe381Leu | missense_variant | 5/7 | 1 | NM_001319217.2 | ENSP00000369050 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;D;D;D;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T;T;.;.;.;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;N;N;N;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
.;.;T;T;T;T;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
0.45, 0.82
.;B;P;P;P;B;.;.
Vest4
MutPred
0.56
.;Gain of catalytic residue at F381 (P = 0.04);Gain of catalytic residue at F381 (P = 0.04);Gain of catalytic residue at F381 (P = 0.04);Gain of catalytic residue at F381 (P = 0.04);Gain of catalytic residue at F381 (P = 0.04);.;.;
MVP
MPC
0.083
ClinPred
D
GERP RS
Varity_R
gMVP
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