19-40850376-T-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1
The NM_000762.6(CYP2A6):āc.51A>Gā(p.Val17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,609,596 control chromosomes in the GnomAD database, including 456,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).
Frequency
Genomes: š 0.76 ( 44365 hom., cov: 31)
Exomes š: 0.74 ( 411757 hom. )
Consequence
CYP2A6
NM_000762.6 synonymous
NM_000762.6 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.06
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
BP6
Variant 19-40850376-T-C is Benign according to our data. Variant chr19-40850376-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.06 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP2A6 | NM_000762.6 | c.51A>G | p.Val17= | synonymous_variant | 1/9 | ENST00000301141.10 | NP_000753.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP2A6 | ENST00000301141.10 | c.51A>G | p.Val17= | synonymous_variant | 1/9 | 1 | NM_000762.6 | ENSP00000301141 | P1 | |
CYP2A6 | ENST00000596719.5 | n.65A>G | non_coding_transcript_exon_variant | 1/6 | 1 | |||||
CYP2A6 | ENST00000600495.1 | c.51A>G | p.Val17= | synonymous_variant, NMD_transcript_variant | 1/6 | 1 | ENSP00000472905 |
Frequencies
GnomAD3 genomes AF: 0.760 AC: 114470AN: 150552Hom.: 44326 Cov.: 31
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GnomAD3 exomes AF: 0.755 AC: 189110AN: 250430Hom.: 73388 AF XY: 0.747 AC XY: 101112AN XY: 135348
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GnomAD4 exome AF: 0.743 AC: 1083821AN: 1458930Hom.: 411757 Cov.: 74 AF XY: 0.740 AC XY: 536953AN XY: 725792
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GnomAD4 genome AF: 0.760 AC: 114554AN: 150666Hom.: 44365 Cov.: 31 AF XY: 0.760 AC XY: 55886AN XY: 73494
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at