Variant rs2278970 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001319217.2(CYP1A1):c.1388C>T(p.Ala463Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CYP1A1
NM_001319217.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.447

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]

CYP1A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1A1	NM_001319217.2 linkuse as main transcript	c.1388C>T	p.Ala463Val	missense_variant	7/7	ENST00000379727.8	NP_001306146.1	P04798-1A0N0X8
CYP1A1	NM_000499.5 linkuse as main transcript	c.1388C>T	p.Ala463Val	missense_variant	7/7		NP_000490.1	P04798-1A0N0X8
CYP1A1	NM_001319216.2 linkuse as main transcript	c.1301C>T	p.Ala434Val	missense_variant	6/6		NP_001306145.1	P04798E7EMT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1A1	ENST00000379727.8 linkuse as main transcript	c.1388C>T	p.Ala463Val	missense_variant	7/7	1	NM_001319217.2	ENSP00000369050.3		P04798-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251440

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727240

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:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

T;T;D;D;D;T

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D;.;.;.

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.97

D;D;D;D;D;D

MetaSVM

Pathogenic

0.96

MutationAssessor

Pathogenic

3.8

.;.;H;H;H;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.9

.;.;D;D;D;D

REVEL

Uncertain

0.64

Sift

Uncertain

0.0010

.;.;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D

Polyphen

0.98, 0.99

.;D;D;D;D;D

Vest4

0.52

MutPred

0.89

.;.;Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);.;

MVP

1.0

MPC

0.22

ClinPred

1.0

GERP RS

-0.30

Varity_R

0.63

gMVP

0.82

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over