dbSNP rs2470890: CYP1A2:p.Asn516Asn (chr15-74755085-T-C) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000761.5(CYP1A2):c.1548T>C(p.Asn516Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,602,572 control chromosomes in the GnomAD database, including 173,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.57 ( 29243 hom., cov: 32)

Exomes 𝑓: 0.41 ( 144292 hom. )

Consequence

CYP1A2
NM_000761.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.219

Publications

154 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 15-74755085-T-C is Benign according to our data. Variant chr15-74755085-T-C is described in ClinVar as Benign. ClinVar VariationId is 768718.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.219 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1A2	NM_000761.5 link	c.1548T>C	p.Asn516Asn	synonymous_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.1548T>C	p.Asn516Asn	synonymous_variant	Exon 7 of 7	1	NM_000761.5	ENSP00000342007.4		P05177

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86870

AN:

151998

Hom.:

29170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.885

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.650

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.843

Gnomad SAS

AF:

0.807

Gnomad FIN

AF:

0.441

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.552

GnomAD4 exome

AF:

0.414

AC:

600555

AN:

1450458

Hom.:

144292

Cov.:

AF XY:

0.423

AC XY:

304798

AN XY:

719852

show subpopulations

African (AFR)

AF:

0.904

AC:

30129

AN:

33344

American (AMR)

AF:

0.728

AC:

32480

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

11653

AN:

26080

East Asian (EAS)

AF:

0.814

AC:

32161

AN:

39510

South Asian (SAS)

AF:

0.791

AC:

68116

AN:

86152

European-Finnish (FIN)

AF:

0.434

AC:

21692

AN:

49934

Middle Eastern (MID)

AF:

0.497

AC:

2757

AN:

5546

European-Non Finnish (NFE)

AF:

0.338

AC:

373912

AN:

1105318

Other (OTH)

AF:

0.461

AC:

27655

AN:

59950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

19878

39756

59633

79511

99389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12592

25184

37776

50368

62960

<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:

0.572

AC:

87007

AN:

152114

Hom.:

29243

Cov.:

AF XY:

0.585

AC XY:

43463

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.886

AC:

36779

AN:

41522

American (AMR)

AF:

0.650

AC:

9940

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.451

AC:

1563

AN:

3466

East Asian (EAS)

AF:

0.843

AC:

4353

AN:

5162

South Asian (SAS)

AF:

0.808

AC:

3901

AN:

4828

European-Finnish (FIN)

AF:

0.441

AC:

4652

AN:

10548

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.353

AC:

24013

AN:

67988

Other (OTH)

AF:

0.557

AC:

1176

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1525

3050

4576

6101

7626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.431

Hom.:

50971

Bravo

AF:

0.593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.7

(source)

PhyloP100

0.22

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over