Variant rs72547516 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000761.5(CYP1A2):c.1156A>G(p.Ile386Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,613,764 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I386F) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 7 hom. )

Consequence

CYP1A2
NM_000761.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.28

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020976245).

BS2

High AC in GnomAd4 at 115 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP1A2	NM_000761.5 linkuse as main transcript	c.1156A>G	p.Ile386Val	missense_variant	5/7	ENST00000343932.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP1A2	ENST00000343932.5 linkuse as main transcript	c.1156A>G	p.Ile386Val	missense_variant	5/7	1	NM_000761.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000750

AC:

114

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000677

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00131

AC:

329

AN:

251252

Hom.:

AF XY:

0.00155

AC XY:

211

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00588

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.000713

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00110

AC:

1602

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

878

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00588

Gnomad4 FIN exome

AF:

0.00273

Gnomad4 NFE exome

AF:

0.000794

Gnomad4 OTH exome

AF:

0.000961

GnomAD4 genome

AF:

0.000756

AC:

115

AN:

152056

Hom.:

Cov.:

AF XY:

0.000902

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00457

Gnomad4 FIN

AF:

0.00321

Gnomad4 NFE

AF:

0.000677

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.000397

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00122

AC:

148

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.26

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

M_CAP

Benign

0.013

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.84

REVEL

Benign

0.20

Sift

Uncertain

0.0080

Sift4G

Benign

0.081

Vest4

0.45

MVP

0.45

MPC

0.059

ClinPred

0.048

GERP RS

3.8

Varity_R

0.52

gMVP

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over