15-74722964-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001319217.2(CYP1A1):c.134G>A(p.Gly45Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,614,170 control chromosomes in the GnomAD database, including 529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0049 ( 53 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 476 hom. )

Consequence

CYP1A1
NM_001319217.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.97

Publications

53 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020495355).

BP6

Variant 15-74722964-C-T is Benign according to our data. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-74722964-C-T is described in CliVar as Benign. Clinvar id is 3058859.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1A1	NM_001319217.2 link	c.134G>A	p.Gly45Asp	missense_variant	Exon 2 of 7	ENST00000379727.8	NP_001306146.1	P04798-1A0N0X8
CYP1A1	NM_000499.5 link	c.134G>A	p.Gly45Asp	missense_variant	Exon 2 of 7		NP_000490.1	P04798-1A0N0X8
CYP1A1	NM_001319216.2 link	c.134G>A	p.Gly45Asp	missense_variant	Exon 2 of 6		NP_001306145.1	P04798E7EMT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1A1	ENST00000379727.8 link	c.134G>A	p.Gly45Asp	missense_variant	Exon 2 of 7	1	NM_001319217.2	ENSP00000369050.3		P04798-1

Frequencies

GnomAD3 genomes

AF:

0.00494

AC:

751

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.0108

AC:

2707

AN:

251386

AF XY:

0.0100

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00448

AC:

6555

AN:

1461878

Hom.:

476

Cov.:

AF XY:

0.00433

AC XY:

3147

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000268

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.146

AC:

5802

AN:

39700

South Asian (SAS)

AF:

0.00220

AC:

190

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000558

AC:

AN:

1112000

Other (OTH)

AF:

0.00796

AC:

481

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

380

761

1141

1522

1902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00494

AC:

752

AN:

152292

Hom.:

Cov.:

AF XY:

0.00571

AC XY:

425

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41560

American (AMR)

AF:

0.000849

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.132

AC:

684

AN:

5166

South Asian (SAS)

AF:

0.00601

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68036

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00431

Hom.:

228

Bravo

AF:

0.00645

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0104

AC:

1261

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CYP1A1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;T;D;D;D;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.68

T;T;T;.;.;.

MetaRNN

Benign

0.0020

T;T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Pathogenic

3.8

.;.;H;H;H;.

PhyloP100

3.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.5

.;.;N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.043

.;.;D;D;D;D

Sift4G

Uncertain

0.038

D;D;D;D;D;D

Polyphen

0.85, 0.84

.;P;P;P;P;P

Vest4

0.51

MPC

0.20

ClinPred

0.13

GERP RS

4.7

Varity_R

0.86

gMVP

0.76

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over