19-40849290-G-C

Variant names:

• chr19-40849290-G-C
• rs7250713
• NM_000762.6:c.344-527C>G

Variant summary

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

The NM_000762.6(CYP2A6):​c.344-527C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 150,198 control chromosomes in the GnomAD database, including 20,294 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 0.50 (20294 hom., cov: 28)
• Consequence: CYP2A6 NM_000762.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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]

ENSG00000268797 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-40849290-G-C is Benign according to our data. Variant chr19-40849290-G-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2A6	NM_000762.6	c.344-527C>G		intron_variant	Intron 2 of 8	ENST00000301141.10	NP_000753.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2A6	ENST00000301141.10	c.344-527C>G		intron_variant	Intron 2 of 8	1	NM_000762.6	ENSP00000301141.4
CYP2A6	ENST00000596719.5	n.195-527C>G		intron_variant	Intron 1 of 5	1
CYP2A6	ENST00000600495.1	n.*156-527C>G		intron_variant	Intron 2 of 5	1		ENSP00000472905.1
ENSG00000268797	ENST00000601627.1	n.118-42701G>C		intron_variant	Intron 1 of 3	3		ENSP00000469533.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 74893 AN: 150088 Hom.: 20275 Cov.: 28

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.493

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.499 AC: 74935 AN: 150198 Hom.: 20294 Cov.: 28 AF XY: 0.504 AC XY: 36878 AN XY: 73228

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.493

Alfa AF: 0.528 Hom.: 2793

Bravo AF: 0.489

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.61

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: rs7250713; hg19: chr19-41355195;