rs5031016
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000762.6(CYP2A6):āc.1412T>Cā(p.Ile471Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00603 in 151,060 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: š 0.0060 ( 25 hom., cov: 30)
Exomes š: 0.0055 ( 85 hom. )
Failed GnomAD Quality Control
Consequence
CYP2A6
NM_000762.6 missense
NM_000762.6 missense
Scores
1
5
10
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.84
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0038813949).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP2A6 | NM_000762.6 | c.1412T>C | p.Ile471Thr | missense_variant | 9/9 | ENST00000301141.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP2A6 | ENST00000301141.10 | c.1412T>C | p.Ile471Thr | missense_variant | 9/9 | 1 | NM_000762.6 | P1 | |
CYP2A6 | ENST00000599960.1 | n.331T>C | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00608 AC: 918AN: 150944Hom.: 25 Cov.: 30
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GnomAD3 exomes AF: 0.00813 AC: 2023AN: 248754Hom.: 13 AF XY: 0.00752 AC XY: 1011AN XY: 134460
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00549 AC: 8004AN: 1457534Hom.: 85 Cov.: 33 AF XY: 0.00545 AC XY: 3952AN XY: 724966
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.00603 AC: 911AN: 151060Hom.: 25 Cov.: 30 AF XY: 0.00628 AC XY: 463AN XY: 73760
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Pathogenic
D
Vest4
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at