dbSNP rs72547586: CYP2A13:p.Arg64Ser (chr19-41088938-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000766.5(CYP2A13):c.190C>A(p.Arg64Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,876 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

CYP2A13
NM_000766.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.642

Publications

12 publications found

Variant links:

Genes affected

CYP2A13 (HGNC:2608): (cytochrome P450 family 2 subfamily A member 13) 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. This protein localizes to the endoplasmic reticulum. Although its endogenous substrate has not been determined, it is known to metabolize 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a major nitrosamine specific to tobacco. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]

CYP2A13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044074208).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000766.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2A13	NM_000766.5	MANE Select	c.190C>A	p.Arg64Ser	missense	Exon 2 of 9	NP_000757.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2A13	ENST00000330436.4	TSL:1 MANE Select	c.190C>A	p.Arg64Ser	missense	Exon 2 of 9	ENSP00000332679.1	Q16696
	CYP2A13	ENST00000874269.1		c.190C>A	p.Arg64Ser	missense	Exon 2 of 9	ENSP00000544328.1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000837

AC:

AN:

250966

AF XY:

0.0000664

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461718

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

33472

American (AMR)

AF:

0.0000447

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111928

Other (OTH)

AF:

0.0000497

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000263

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.000941

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.043

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.58

M_CAP

Benign

0.026

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.5

PhyloP100

-0.64

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.12

Sift4G

Benign

0.12

Polyphen

0.47

Vest4

0.25

MVP

0.69

MPC

0.13

ClinPred

0.023

GERP RS

2.3

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.60

gMVP

0.41

Mutation Taster

=92/8

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