NM_000767.5:c.20T>C

Variant names:

• chr19-40991325-T-C
• NM_000767.5:c.20T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000767.5(CYP2B6):​c.20T>C​(p.Leu7Pro) 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: 31)
• Consequence: CYP2B6 NM_000767.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.20T>C	p.Leu7Pro	missense_variant	Exon 1 of 9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.20T>C	p.Leu7Pro	missense_variant	Exon 1 of 9	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000598834.2	n.-80T>C		upstream_gene_variant		5		ENSP00000496294.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20T>C (p.L7P) alteration is located in exon 1 (coding exon 1) of the CYP2B6 gene. This alteration results from a T to C substitution at nucleotide position 20, causing the leucine (L) at amino acid position 7 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Benign	0.046	T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.0073	T
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.2	.;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.021	.;D
Sift4G	Uncertain	0.020	.;D
Polyphen		1.0	D;D
Vest4		0.76
MutPred		0.79		Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);
MVP		0.75
MPC		0.10
ClinPred		0.58	D
GERP RS		3.1
Varity_R		0.64
gMVP		0.55

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: chr19-41497230;