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GeneBe

rs8192720

chr19-40850405-G-Achr19-40850405-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000762.6(CYP2A6):c.22C>T(p.Leu8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,609,772 control chromosomes in the GnomAD database, including 2,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.019 ( 244 hom., cov: 31)
Exomes 𝑓: 0.011 ( 2146 hom. )

Consequence

CYP2A6
NM_000762.6 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53
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 -14 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=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-40850405-G-A is Benign according to our data. Variant chr19-40850405-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=1.53 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP2A6NM_000762.6 linkuse as main transcriptc.22C>T p.Leu8= synonymous_variant 1/9 ENST00000301141.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP2A6ENST00000301141.10 linkuse as main transcriptc.22C>T p.Leu8= synonymous_variant 1/91 NM_000762.6 P1
CYP2A6ENST00000596719.5 linkuse as main transcriptn.36C>T non_coding_transcript_exon_variant 1/61
CYP2A6ENST00000600495.1 linkuse as main transcriptc.22C>T p.Leu8= synonymous_variant, NMD_transcript_variant 1/61

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0188
AC:
2849
AN:
151164
Hom.:
244
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0271
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.00680
Gnomad ASJ
AF:
0.0191
Gnomad EAS
AF:
0.188
Gnomad SAS
AF:
0.0101
Gnomad FIN
AF:
0.0308
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00318
Gnomad OTH
AF:
0.0193
GnomAD3 exomes
AF:
0.0227
AC:
5675
AN:
250066
Hom.:
711
AF XY:
0.0210
AC XY:
2831
AN XY:
135128
show subpopulations
Gnomad AFR exome
AF:
0.0283
Gnomad AMR exome
AF:
0.00432
Gnomad ASJ exome
AF:
0.0231
Gnomad EAS exome
AF:
0.191
Gnomad SAS exome
AF:
0.00427
Gnomad FIN exome
AF:
0.0338
Gnomad NFE exome
AF:
0.00378
Gnomad OTH exome
AF:
0.0146
GnomAD4 exome
AF:
0.0111
AC:
16203
AN:
1458496
Hom.:
2146
Cov.:
34
AF XY:
0.0110
AC XY:
7958
AN XY:
725560
show subpopulations
Gnomad4 AFR exome
AF:
0.0285
Gnomad4 AMR exome
AF:
0.00464
Gnomad4 ASJ exome
AF:
0.0227
Gnomad4 EAS exome
AF:
0.222
Gnomad4 SAS exome
AF:
0.00475
Gnomad4 FIN exome
AF:
0.0324
Gnomad4 NFE exome
AF:
0.00247
Gnomad4 OTH exome
AF:
0.0162
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0188
AC:
2848
AN:
151276
Hom.:
244
Cov.:
31
AF XY:
0.0206
AC XY:
1523
AN XY:
73864
show subpopulations
Gnomad4 AFR
AF:
0.0271
Gnomad4 AMR
AF:
0.00679
Gnomad4 ASJ
AF:
0.0191
Gnomad4 EAS
AF:
0.187
Gnomad4 SAS
AF:
0.00989
Gnomad4 FIN
AF:
0.0308
Gnomad4 NFE
AF:
0.00318
Gnomad4 OTH
AF:
0.0192
Alfa
AF:
0.00930
Hom.:
35
Bravo
AF:
0.0190
Asia WGS
AF:
0.0890
AC:
303
AN:
3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
6.1
Dann
Benign
0.62

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.

Other links and lift over

dbSNP: rs8192720; hg19: chr19-41356310; COSMIC: COSV56534090; API