Genetic Variant CYP1A2:c.*1047dupT (chr15-74756121-G-GT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000761.5(CYP1A2):c.*1047dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.046 ( 239 hom., cov: 0)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

CYP1A2
NM_000761.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.254

Publications

1 publications found

Variant links:

Genes affected

CYP1A2 (HGNC:2596): (cytochrome P450 family 1 subfamily A member 2) This gene 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. The protein encoded by this gene 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. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. [provided by RefSeq, Jul 2008]

CYP1A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1A2	NM_000761.5 link	c.*1047dupT		3_prime_UTR_variant	Exon 7 of 7	ENST00000343932.5	NP_000752.2	P05177

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1A2	ENST00000343932.5 link	c.*1047dupT		3_prime_UTR_variant	Exon 7 of 7	1	NM_000761.5	ENSP00000342007.4		P05177

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

5934

AN:

129294

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.0572

Gnomad AMR

AF:

0.0492

Gnomad ASJ

AF:

0.0768

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.0583

Gnomad MID

AF:

0.0725

Gnomad NFE

AF:

0.0376

Gnomad OTH

AF:

0.0556

GnomAD4 exome

AF:

0.143

AC:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.143

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0459

AC:

5936

AN:

129296

Hom.:

239

Cov.:

AF XY:

0.0504

AC XY:

3133

AN XY:

62188

show subpopulations

African (AFR)

AF:

0.0194

AC:

647

AN:

33346

American (AMR)

AF:

0.0493

AC:

634

AN:

12856

Ashkenazi Jewish (ASJ)

AF:

0.0768

AC:

245

AN:

3192

East Asian (EAS)

AF:

0.151

AC:

659

AN:

4368

South Asian (SAS)

AF:

0.213

AC:

857

AN:

4030

European-Finnish (FIN)

AF:

0.0583

AC:

416

AN:

7138

Middle Eastern (MID)

AF:

0.0661

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.0376

AC:

2313

AN:

61530

Other (OTH)

AF:

0.0576

AC:

102

AN:

1772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

232

465

697

930

1162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0118

Hom.:

443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism

(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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15-74756121-GTTT-GTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over