NM_001319217.2:c.1143C>A

Variant names:

• chr15-74721222-G-T
• rs2856833
• NM_001319217.2:c.1143C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001319217.2(CYP1A1):​c.1143C>A​(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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319217.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A1	NM_001319217.2	MANE Select	c.1143C>A	p.Phe381Leu	missense	Exon 5 of 7	NP_001306146.1
	CYP1A1	NM_000499.5		c.1143C>A	p.Phe381Leu	missense	Exon 5 of 7	NP_000490.1
	CYP1A1	NM_001319216.2		c.1143C>A	p.Phe381Leu	missense	Exon 5 of 6	NP_001306145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A1	ENST00000379727.8	TSL:1 MANE Select	c.1143C>A	p.Phe381Leu	missense	Exon 5 of 7	ENSP00000369050.3
	CYP1A1	ENST00000395048.6	TSL:1	c.1143C>A	p.Phe381Leu	missense	Exon 5 of 7	ENSP00000378488.2
	CYP1A1	ENST00000567032.5	TSL:1	c.1143C>A	p.Phe381Leu	missense	Exon 5 of 7	ENSP00000456585.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000237 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.74
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.57
Sift	Benign	0.056	T
Sift4G	Benign	0.18	T
Polyphen		0.45	B
Vest4		0.69
MutPred		0.56		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)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2856833; hg19: chr15-75013563;