dbSNP rs56141902: CYP1A2:c.*854G>A (chr15-74755942-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000761.5(CYP1A2):c.*854G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 147,784 control chromosomes in the GnomAD database, including 1 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.

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0055 ( 0 hom. )

Consequence

CYP1A2
NM_000761.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000761.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A2	NM_000761.5	MANE Select	c.*854G>A		3_prime_UTR	Exon 7 of 7	NP_000752.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A2	ENST00000343932.5	TSL:1 MANE Select	c.*854G>A		3_prime_UTR	Exon 7 of 7	ENSP00000342007.4

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

249

AN:

147480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000354

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000406

Gnomad ASJ

AF:

0.00407

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0262

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.000996

GnomAD4 exome

AF:

0.00549

AC:

AN:

182

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

AN XY:

138

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

132

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.825

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00169

AC:

249

AN:

147602

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

134

AN XY:

72026

show subpopulations

African (AFR)

AF:

0.000353

AC:

AN:

39686

American (AMR)

AF:

0.000405

AC:

AN:

14804

Ashkenazi Jewish (ASJ)

AF:

0.00407

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

4920

South Asian (SAS)

AF:

0.0263

AC:

121

AN:

4604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.00138

AC:

AN:

66882

Other (OTH)

AF:

0.000985

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00164

Hom.:

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

3.9

(source)

DANN

Benign

0.80

PhyloP100

-1.1

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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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