Genetic Variant CYP2B6:p.Arg487Ser (chr19-41016810-CGC-TCA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_000767.5(CYP2B6):c.1459_1461delCGCinsTCA (p.Arg487Ser) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. 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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.611

Publications

0 publications found

Variant links:

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 links:

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new If you want to explore the variant's impact on the transcript NM_000767.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CYP2B6 NM_000767.5	MANE Select	c.1459_1461delCGCinsTCA p.Arg487Ser	missense	N/A	Prot: NP_000758.1 UniProt: P20813-1

CYP2B6 NM_000767.5

MANE Select

HGVSc / HGVSpc.1459_1461delCGCinsTCAp.Arg487Ser

Exon rankN/A

missense

Prot: NP_000758.1UniProt: P20813-1

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
CYP2B6 ENST00000324071.10	TSL:1MANE Select	c.1459_1461delCGCinsTCA p.Arg487Ser	missense	N/A	Prot: ENSP00000324648.2 UniProt: P20813-1
CYP2B6 ENST00000597612.1	TSL:1	n.812_814delCGCinsTCA	non_coding_transcript_exon	Exon 3 of 3	Prot:
CYP2B6 ENST00000863358.1		c.1114_1116delCGCinsTCA p.Arg372Ser	missense	N/A	Prot: ENSP00000533417.1 UniProt: A0ACI8QFV7

CYP2B6 ENST00000324071.10

TSL:1MANE Select

HGVSc / HGVSpc.1459_1461delCGCinsTCAp.Arg487Ser

Exon rankN/A

missense

Prot: ENSP00000324648.2UniProt: P20813-1

CYP2B6 ENST00000597612.1

TSL:1

HGVSc / HGVSpn.812_814delCGCinsTCA

Exon rankExon 3 of 3

non_coding_transcript_exon

Prot:

CYP2B6 ENST00000863358.1

HGVSc / HGVSpc.1114_1116delCGCinsTCAp.Arg372Ser

Exon rankN/A

missense

Prot: ENSP00000533417.1UniProt: A0ACI8QFV7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	-0.61

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence