19-40848304-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000762.6(CYP2A6):c.569G>T(p.Arg190Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000454 in 1,611,882 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00048 ( 28 hom. )

Consequence

CYP2A6
NM_000762.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.59

Variant links:

Genes affected

CYP2A6 (HGNC:2610): (cytochrome P450 family 2 subfamily A member 6) This gene, CYP2A6, 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. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to hydroxylate coumarin, and also metabolizes nicotine, aflatoxin B1, nitrosamines, and some pharmaceuticals. Individuals with certain allelic variants are said to have a poor metabolizer phenotype, meaning they do not efficiently metabolize coumarin or nicotine. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6. [provided by RefSeq, Jul 2008]

CYP2A6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.067304075).

BP6

Variant 19-40848304-C-A is Benign according to our data. Variant chr19-40848304-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 739786.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2A6	NM_000762.6 linkuse as main transcript	c.569G>T	p.Arg190Leu	missense_variant	4/9	ENST00000301141.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CYP2A6	ENST00000301141.10 linkuse as main transcript	c.569G>T	p.Arg190Leu	missense_variant	4/9	1	NM_000762.6	P1
CYP2A6	ENST00000596719.5 linkuse as main transcript	n.420G>T		non_coding_transcript_exon_variant	3/6	1
CYP2A6	ENST00000600495.1 linkuse as main transcript	c.*381G>T		3_prime_UTR_variant, NMD_transcript_variant	4/6	1

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

151454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00753

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000972

AC:

244

AN:

251158

Hom.:

AF XY:

0.00139

AC XY:

189

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00788

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000475

AC:

694

AN:

1460316

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

507

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000156

Gnomad4 SAS exome

AF:

0.00771

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.000244

AC:

AN:

151566

Hom.:

Cov.:

AF XY:

0.000405

AC XY:

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00754

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000236

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.00113

AC:

137

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.013

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Vest4

0.83

MutPred

0.90

Gain of ubiquitination at K194 (P = 0.0719);

MVP

0.46

MPC

0.15

ClinPred

0.28

GERP RS

2.7

gMVP

0.55

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over