15-74721022-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001319217.2(CYP1A1):āc.1198T>Cā(p.Tyr400His) variant causes a missense change. The variant allele was found at a frequency of 0.0000607 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 32)
Exomes š: 0.000064 ( 0 hom. )
Consequence
CYP1A1
NM_001319217.2 missense
NM_001319217.2 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 6.16
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 | UniProt |
---|---|---|---|---|---|---|---|
CYP1A1 | NM_001319217.2 | c.1198T>C | p.Tyr400His | missense_variant | 6/7 | ENST00000379727.8 | |
CYP1A1 | NM_000499.5 | c.1198T>C | p.Tyr400His | missense_variant | 6/7 | ||
CYP1A1 | NM_001319216.2 | c.1166+177T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP1A1 | ENST00000379727.8 | c.1198T>C | p.Tyr400His | missense_variant | 6/7 | 1 | NM_001319217.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251476Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135910
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GnomAD4 exome AF: 0.0000636 AC: 93AN: 1461866Hom.: 0 Cov.: 32 AF XY: 0.0000633 AC XY: 46AN XY: 727238
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2023 | The c.1198T>C (p.Y400H) alteration is located in exon 6 (coding exon 5) of the CYP1A1 gene. This alteration results from a T to C substitution at nucleotide position 1198, causing the tyrosine (Y) at amino acid position 400 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.;.;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;L;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
.;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.18
.;B;B;B;.;.
Vest4
MVP
MPC
0.16
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at