19-40994084-A-G

Variant names:

• chr19-40994084-A-G
• rs2014141
• NM_000767.5:c.171+2608A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):​c.171+2608A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,992 control chromosomes in the GnomAD database, including 38,518 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 0.70 (38518 hom., cov: 30)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 14 publications found

Genes affected

CYP2B6 (HGNC:2615): (cytochrome P450 family 2 subfamily B member 6) This gene, CYP2B6, 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 metabolize some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide. Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000767.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	NM_000767.5	MANE Select	c.171+2608A>G		intron	N/A	NP_000758.1	P20813-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	ENST00000324071.10	TSL:1 MANE Select	c.171+2608A>G		intron	N/A	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000863358.1		c.171+2608A>G		intron	N/A	ENSP00000533417.1
	CYP2B6	ENST00000863357.1		c.171+2608A>G		intron	N/A	ENSP00000533416.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105913 AN: 151874 Hom.: 38468 Cov.: 30

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.698 AC: 106022 AN: 151992 Hom.: 38518 Cov.: 30 AF XY: 0.700 AC XY: 51958 AN XY: 74276

African (AFR) AF: 0.900 AC: 37335 AN: 41466

American (AMR) AF: 0.758 AC: 11570 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2125 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3391 AN: 5174

South Asian (SAS) AF: 0.753 AC: 3619 AN: 4806

European-Finnish (FIN) AF: 0.586 AC: 6184 AN: 10550

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.585 AC: 39738 AN: 67962

Other (OTH) AF: 0.689 AC: 1449 AN: 2102

Alfa AF: 0.630 Hom.: 52178

Bravo AF: 0.717

Asia WGS AF: 0.714 AC: 2480 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.6
DANN	Benign	0.36
PhyloP100		-0.85
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: rs2014141; hg19: chr19-41499989;