Genetic Variant NM_000761.5:c.1043-65G>C (chr15-74752059-G-C) – 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.1043-65G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 1,603,436 control chromosomes in the GnomAD database, including 3,192 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 0.041 ( 259 hom., cov: 32)

Exomes 𝑓: 0.043 ( 2933 hom. )

Consequence

CYP1A2
NM_000761.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.45

Publications

21 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:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1A2	NM_000761.5 link	c.1043-65G>C		intron_variant	Intron 4 of 6	ENST00000343932.5	NP_000752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1A2	ENST00000343932.5 link	c.1043-65G>C		intron_variant	Intron 4 of 6	1	NM_000761.5	ENSP00000342007.4

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

6201

AN:

152132

Hom.:

254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0291

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.0326

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0289

Gnomad OTH

AF:

0.0440

GnomAD4 exome

AF:

0.0435

AC:

63122

AN:

1451186

Hom.:

2933

Cov.:

AF XY:

0.0476

AC XY:

34310

AN XY:

721234

show subpopulations

African (AFR)

AF:

0.0255

AC:

847

AN:

33280

American (AMR)

AF:

0.0416

AC:

1820

AN:

43768

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

1026

AN:

25112

East Asian (EAS)

AF:

0.149

AC:

5923

AN:

39632

South Asian (SAS)

AF:

0.187

AC:

15806

AN:

84328

European-Finnish (FIN)

AF:

0.0305

AC:

1604

AN:

52608

Middle Eastern (MID)

AF:

0.0426

AC:

243

AN:

5706

European-Non Finnish (NFE)

AF:

0.0293

AC:

32432

AN:

1106816

Other (OTH)

AF:

0.0571

AC:

3421

AN:

59936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3172

6343

9515

12686

15858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1492

2984

4476

5968

7460

<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:

0.0409

AC:

6224

AN:

152250

Hom.:

259

Cov.:

AF XY:

0.0448

AC XY:

3336

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0291

AC:

1207

AN:

41524

American (AMR)

AF:

0.0409

AC:

626

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0435

AC:

151

AN:

3470

East Asian (EAS)

AF:

0.152

AC:

785

AN:

5176

South Asian (SAS)

AF:

0.207

AC:

998

AN:

4824

European-Finnish (FIN)

AF:

0.0326

AC:

346

AN:

10618

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0289

AC:

1964

AN:

68018

Other (OTH)

AF:

0.0511

AC:

108

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

289

578

866

1155

1444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0158

Hom.:

Bravo

AF:

0.0369

Asia WGS

AF:

0.235

AC:

814

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0050

(source)

DANN

Benign

0.63

PhyloP100

-2.5

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over