19-41004015-T-A

Position:

• chr19-41004015-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000767.5(CYP2B6):​c.186T>A​(p.Tyr62*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as drug response (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CYP2B6 NM_000767.5 stop_gained
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -3.41

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.186T>A	p.Tyr62*	stop_gained	2/9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.186T>A	p.Tyr62*	stop_gained	2/9	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000593831.1	c.-43T>A		5_prime_UTR_variant	1/5	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.87T>A		non_coding_transcript_exon_variant	2/10	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Efavirenz response Other:1

drug response, no assertion criteria provided

research

Institute of Microbiology; University Hospital and Univeristy of Lausanne

Oct 11, 2012

- This variant was associated with very high efavirenz plasma levels in a HIV+individual

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Benign	-0.61
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
MutationTaster	Benign	1.0	A;A
Vest4		0.69
GERP RS		-5.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs281864907; hg19: chr19-41509920;