Variant 19-40844725-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000762.6(CYP2A6):c.1209T>C(p.Ser403=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 1,611,118 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0064 ( 105 hom. )

Consequence

CYP2A6
NM_000762.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.84

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 19-40844725-A-G is Benign according to our data. Variant chr19-40844725-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2649913.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-40844725-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.84 with no splicing effect.

BS2

High AC in GnomAd4 at 732 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2A6	NM_000762.6 linkuse as main transcript	c.1209T>C	p.Ser403=	synonymous_variant	8/9	ENST00000301141.10	NP_000753.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2A6	ENST00000301141.10 linkuse as main transcript	c.1209T>C	p.Ser403=	synonymous_variant	8/9	1	NM_000762.6	ENSP00000301141	P1
CYP2A6	ENST00000599960.1 linkuse as main transcript	n.128T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00482

AC:

729

AN:

151336

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00881

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00121

Gnomad SAS

AF:

0.00105

Gnomad FIN

AF:

0.00408

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00631

Gnomad OTH

AF:

0.00481

GnomAD3 exomes

AF:

0.00511

AC:

1284

AN:

251054

Hom.:

AF XY:

0.00510

AC XY:

692

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00599

Gnomad ASJ exome

AF:

0.00506

Gnomad EAS exome

AF:

0.00143

Gnomad SAS exome

AF:

0.000818

Gnomad FIN exome

AF:

0.00615

Gnomad NFE exome

AF:

0.00678

Gnomad OTH exome

AF:

0.00816

GnomAD4 exome

AF:

0.00642

AC:

9373

AN:

1459666

Hom.:

105

Cov.:

AF XY:

0.00633

AC XY:

4600

AN XY:

726168

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00615

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.000416

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.00652

Gnomad4 NFE exome

AF:

0.00730

Gnomad4 OTH exome

AF:

0.00607

GnomAD4 genome

AF:

0.00483

AC:

732

AN:

151452

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

335

AN XY:

73982

show subpopulations

Gnomad4 AFR

AF:

0.00131

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00121

Gnomad4 SAS

AF:

0.00105

Gnomad4 FIN

AF:

0.00408

Gnomad4 NFE

AF:

0.00633

Gnomad4 OTH

AF:

0.00477

Alfa

AF:

0.00310

Hom.:

Bravo

AF:

0.00556

EpiCase

AF:

0.00573

EpiControl

AF:

0.00605

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

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

CYP2A6: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.0

DANN

Benign

0.50

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