19-40847202-T-C

Position:

• chr19-40847202-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000762.6(CYP2A6):​c.655-151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,201,092 control chromosomes in the GnomAD database, including 184,585 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 0.52 (21334 hom., cov: 31)
  • Exomes 𝑓: 0.55 (163251 hom.)
• Consequence: CYP2A6 NM_000762.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-40847202-T-C is Benign according to our data. Variant chr19-40847202-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2A6	NM_000762.6	c.655-151A>G		intron_variant		ENST00000301141.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2A6	ENST00000301141.10	c.655-151A>G		intron_variant		1	NM_000762.6	P1
CYP2A6	ENST00000600495.1	c.*467-151A>G		intron_variant, NMD_transcript_variant		1
CYP2A6	ENST00000596719.5	n.506-151A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78260 AN: 151024 Hom.: 21327 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.549 AC: 576353 AN: 1049954 Hom.: 163251 AF XY: 0.545 AC XY: 281459 AN XY: 516868

Gnomad4 AFR exome AF: 0.390

Gnomad4 AMR exome AF: 0.600

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.559

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.536

GnomAD4 genome AF: 0.518 AC: 78291 AN: 151138 Hom.: 21334 Cov.: 31 AF XY: 0.514 AC XY: 37894 AN XY: 73790

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.525

Alfa AF: 0.553 Hom.: 4114

Bravo AF: 0.516

Asia WGS AF: 0.427 AC: 1465 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.077
DANN	Benign	0.35

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

Other links and lift over

dbSNP: rs56113850; hg19: chr19-41353107; COSMIC: COSV56537913; COSMIC: COSV56537913;