Variant rs2229150 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001319217.2(CYP1A1):c.277C>T(p.Arg93Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 1,614,006 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.00062 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

CYP1A1
NM_001319217.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.290

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12483463).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1A1	NM_001319217.2 link	c.277C>T	p.Arg93Trp	missense_variant	2/7	ENST00000379727.8	NP_001306146.1	P04798-1A0N0X8
CYP1A1	NM_000499.5 link	c.277C>T	p.Arg93Trp	missense_variant	2/7		NP_000490.1	P04798-1A0N0X8
CYP1A1	NM_001319216.2 link	c.277C>T	p.Arg93Trp	missense_variant	2/6		NP_001306145.1	P04798E7EMT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1A1	ENST00000379727.8 link	c.277C>T	p.Arg93Trp	missense_variant	2/7	1	NM_001319217.2	ENSP00000369050.3		P04798-1

Frequencies

GnomAD3 genomes

AF:

0.000624

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000685

AC:

172

AN:

251228

Hom.:

AF XY:

0.000729

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000799

AC:

1168

AN:

1461752

Hom.:

Cov.:

AF XY:

0.000791

AC XY:

575

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.000910

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000624

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000899

Hom.:

Bravo

AF:

0.000582

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000749

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;D;D;D;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.93

D;D;D;.;.;.

M_CAP

Benign

0.057

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

4.1

.;.;H;H;H;.

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-5.6

.;.;D;D;D;D

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

.;.;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;D;D;D

Vest4

0.37

MVP

0.97

MPC

0.034

ClinPred

0.11

GERP RS

-1.1

Varity_R

0.66

gMVP

0.77

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