chr15-74721222-G-C

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

Scores

4
6
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34
Variant links:
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
CYP1A1NM_001319217.2 linkuse as main transcriptc.1143C>G p.Phe381Leu missense_variant 5/7 ENST00000379727.8 NP_001306146.1
CYP1A1NM_000499.5 linkuse as main transcriptc.1143C>G p.Phe381Leu missense_variant 5/7 NP_000490.1
CYP1A1NM_001319216.2 linkuse as main transcriptc.1143C>G p.Phe381Leu missense_variant 5/6 NP_001306145.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP1A1ENST00000379727.8 linkuse as main transcriptc.1143C>G p.Phe381Leu missense_variant 5/71 NM_001319217.2 ENSP00000369050 P1P04798-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Benign
9.1
DANN
Uncertain
0.98
DEOGEN2
Benign
0.068
T;T;D;D;D;T;.;T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.74
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.86
D;T;T;.;.;.;D;D
M_CAP
Benign
0.074
D
MetaRNN
Uncertain
0.72
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.57
T
MutationAssessor
Benign
0.55
.;.;N;N;N;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-4.5
.;.;D;D;D;D;D;D
REVEL
Uncertain
0.57
Sift
Benign
0.056
.;.;T;T;T;T;D;D
Sift4G
Benign
0.18
T;T;T;T;T;T;T;T
Polyphen
0.45, 0.82
.;B;P;P;P;B;.;.
Vest4
0.69
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
0.90
MPC
0.083
ClinPred
0.78
D
GERP RS
-0.22
Varity_R
0.85
gMVP
0.78

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: rs2856833; hg19: chr15-75013563; API