rs8192720

Variant names:

• chr19-40850405-G-A
• rs8192720
• NM_000762.6:c.22C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-40850405-G-A
• chr19-40850405-G-C
• chr19-40850405-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000762.6(CYP2A6):​c.22C>T​(p.Leu8Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (244 hom., cov: 31)
  • Exomes 𝑓: 0.011 (2146 hom.)
• Consequence: CYP2A6 NM_000762.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• coumarin resistance

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)
• nicotine dependence

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000268797 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=1.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000762.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2A6	NM_000762.6	MANE Select	c.22C>T	p.Leu8Leu	synonymous	Exon 1 of 9	NP_000753.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2A6	ENST00000301141.10	TSL:1 MANE Select	c.22C>T	p.Leu8Leu	synonymous	Exon 1 of 9	ENSP00000301141.4
	CYP2A6	ENST00000596719.5	TSL:1	n.36C>T		non_coding_transcript_exon	Exon 1 of 6
	CYP2A6	ENST00000600495.1	TSL:1	n.22C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000472905.1

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2849 AN: 151164 Hom.: 244 Cov.: 31

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

GnomAD2 exomes AF: 0.0227 AC: 5675 AN: 250066 AF XY: 0.0210

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 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

African (AFR) AF: 0.0285 AC: 954 AN: 33420

American (AMR) AF: 0.00464 AC: 207 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.0227 AC: 593 AN: 26078

East Asian (EAS) AF: 0.222 AC: 8533 AN: 38396

South Asian (SAS) AF: 0.00475 AC: 408 AN: 85972

European-Finnish (FIN) AF: 0.0324 AC: 1726 AN: 53296

Middle Eastern (MID) AF: 0.0101 AC: 58 AN: 5756

European-Non Finnish (NFE) AF: 0.00247 AC: 2749 AN: 1110732

Other (OTH) AF: 0.0162 AC: 975 AN: 60200

GnomAD4 genome AF: 0.0188 AC: 2848 AN: 151276 Hom.: 244 Cov.: 31 AF XY: 0.0206 AC XY: 1523 AN XY: 73864

African (AFR) AF: 0.0271 AC: 1120 AN: 41282

American (AMR) AF: 0.00679 AC: 103 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.0191 AC: 66 AN: 3458

East Asian (EAS) AF: 0.187 AC: 927 AN: 4958

South Asian (SAS) AF: 0.00989 AC: 47 AN: 4754

European-Finnish (FIN) AF: 0.0308 AC: 323 AN: 10494

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00318 AC: 216 AN: 67862

Other (OTH) AF: 0.0192 AC: 40 AN: 2088

Alfa AF: 0.00966 Hom.: 111

Bravo AF: 0.0190

Asia WGS AF: 0.0890 AC: 303 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.62
PhyloP100		1.5
PromoterAI		-0.028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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