chr15-74720646-G-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.1382C>A(p.Thr461Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,614,122 control chromosomes in the GnomAD database, including 1,560 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.030 ( 108 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1452 hom. )

Consequence

CYP1A1
NM_001319217.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.158

Publications

129 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=0.019521713).

BP6

Variant 15-74720646-G-T is Benign according to our data. Variant chr15-74720646-G-T is described in ClinVar as Benign. ClinVar VariationId is 3056253.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP1A1	NM_001319217.2	MANE Select	c.1382C>A	p.Thr461Asn	missense	Exon 7 of 7	NP_001306146.1	P04798-1
CYP1A1	NM_000499.5		c.1382C>A	p.Thr461Asn	missense	Exon 7 of 7	NP_000490.1	A0N0X8
CYP1A1	NM_001319216.2		c.1295C>A	p.Thr432Asn	missense	Exon 6 of 6	NP_001306145.1	E7EMT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP1A1	ENST00000379727.8	TSL:1 MANE Select	c.1382C>A	p.Thr461Asn	missense	Exon 7 of 7	ENSP00000369050.3	P04798-1
CYP1A1	ENST00000395048.6	TSL:1	c.1382C>A	p.Thr461Asn	missense	Exon 7 of 7	ENSP00000378488.2	P04798-1
CYP1A1	ENST00000567032.5	TSL:1	c.1382C>A	p.Thr461Asn	missense	Exon 7 of 7	ENSP00000456585.1	P04798-1

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4543

AN:

152156

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00854

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0922

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0431

Gnomad OTH

AF:

0.0435

GnomAD2 exomes

AF:

0.0309

AC:

7759

AN:

251432

AF XY:

0.0316

show subpopulations

Gnomad AFR exome

AF:

0.00707

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.0864

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0112

Gnomad NFE exome

AF:

0.0427

Gnomad OTH exome

AF:

0.0450

GnomAD4 exome

AF:

0.0402

AC:

58727

AN:

1461848

Hom.:

1452

Cov.:

AF XY:

0.0397

AC XY:

28871

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00869

AC:

291

AN:

33478

American (AMR)

AF:

0.0268

AC:

1198

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0880

AC:

2299

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39700

South Asian (SAS)

AF:

0.0176

AC:

1517

AN:

86258

European-Finnish (FIN)

AF:

0.0116

AC:

620

AN:

53402

Middle Eastern (MID)

AF:

0.125

AC:

721

AN:

5764

European-Non Finnish (NFE)

AF:

0.0445

AC:

49496

AN:

1112002

Other (OTH)

AF:

0.0427

AC:

2578

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

3509

7017

10526

14034

17543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1870

3740

5610

7480

9350

<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:

0.0298

AC:

4541

AN:

152274

Hom.:

108

Cov.:

AF XY:

0.0286

AC XY:

2133

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00852

AC:

354

AN:

41550

American (AMR)

AF:

0.0409

AC:

625

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0922

AC:

320

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0105

AC:

111

AN:

10612

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0431

AC:

2929

AN:

68014

Other (OTH)

AF:

0.0435

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

219

438

658

877

1096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0409

Hom.:

652

Bravo

AF:

0.0320

TwinsUK

AF:

0.0453

AC:

168

ALSPAC

AF:

0.0428

AC:

165

ESP6500AA

AF:

0.00933

AC:

ESP6500EA

AF:

0.0485

AC:

417

ExAC

AF:

0.0305

AC:

3708

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.0495

EpiControl

AF:

0.0504

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CYP1A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.9

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0094

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.29

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.99

PhyloP100

0.16

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.54

REVEL

Benign

0.12

Sift

Benign

0.50

Sift4G

Benign

0.52

Polyphen

0.013

Vest4

0.072

MPC

0.033

ClinPred

0.0027

GERP RS

2.7

Varity_R

0.10

gMVP

0.43

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over