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GeneBe

19-40844695-G-A

Variant summary

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

The NM_000762.6(CYP2A6):c.1239C>T(p.Pro413=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000572 in 1,611,738 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00077 ( 11 hom., cov: 31)
Exomes 𝑓: 0.00055 ( 64 hom. )

Consequence

CYP2A6
NM_000762.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-40844695-G-A is Benign according to our data. Variant chr19-40844695-G-A is described in ClinVar as [Benign]. Clinvar id is 719052.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-40844695-G-A is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.16 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 117 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP2A6NM_000762.6 linkuse as main transcriptc.1239C>T p.Pro413= synonymous_variant 8/9 ENST00000301141.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP2A6ENST00000301141.10 linkuse as main transcriptc.1239C>T p.Pro413= synonymous_variant 8/91 NM_000762.6 P1
CYP2A6ENST00000599960.1 linkuse as main transcriptn.158C>T non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000773
AC:
117
AN:
151382
Hom.:
11
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00605
Gnomad EAS
AF:
0.0159
Gnomad SAS
AF:
0.000629
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000589
Gnomad OTH
AF:
0.00288
GnomAD3 exomes
AF:
0.00170
AC:
426
AN:
251140
Hom.:
38
AF XY:
0.00156
AC XY:
212
AN XY:
135742
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00744
Gnomad EAS exome
AF:
0.0176
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000879
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.000552
AC:
806
AN:
1460240
Hom.:
64
Cov.:
32
AF XY:
0.000559
AC XY:
406
AN XY:
726428
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00769
Gnomad4 EAS exome
AF:
0.0121
Gnomad4 SAS exome
AF:
0.000244
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000270
Gnomad4 OTH exome
AF:
0.00146
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000766
AC:
116
AN:
151498
Hom.:
11
Cov.:
31
AF XY:
0.000851
AC XY:
63
AN XY:
74006
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000197
Gnomad4 ASJ
AF:
0.00605
Gnomad4 EAS
AF:
0.0157
Gnomad4 SAS
AF:
0.000629
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.00286
Alfa
AF:
0.000572
Hom.:
0
Bravo
AF:
0.000918
Asia WGS
AF:
0.00731
AC:
26
AN:
3432
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
Cadd
Benign
2.6
Dann
Benign
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs143336165; hg19: chr19-41350600; API