19-41012803-C-G

Position:

• chr19-41012803-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000767.5(CYP2B6):​c.1282C>G​(p.Pro428Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP2B6 NM_000767.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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]

CYP2B6 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.973

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.1282C>G	p.Pro428Ala	missense_variant	8/9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.1282C>G	p.Pro428Ala	missense_variant	8/9	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1	n.647+318C>G		intron_variant		1
CYP2B6	ENST00000593831.1	c.574C>G	p.Pro192Ala	missense_variant	4/5	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*594-170C>G		intron_variant		5		ENSP00000496294.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T;T;T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	0.059	D
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-7.5	.;D;.
REVEL	Uncertain	0.48
Sift	Benign	0.061	.;T;.
Sift4G	Benign	0.12	.;T;D
Polyphen		1.0	D;D;.
Vest4		0.43, 0.40
MutPred		0.93		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);.;
MVP		0.93
MPC		0.37
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.66
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-41518708;