rs3211371

Variant names:

• chr19-41016810-C-A
• rs3211371
• NM_000767.5:c.1459C>A
• CYP2B6 p.Arg487Ser

Your query was ambiguous. Multiple possible variants found:

• chr19-41016810-C-A
• chr19-41016810-C-G
• chr19-41016810-C-T

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-6 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -6 classification points (ACMG Germline Pathogenicity v2019). BS2BP4_Moderate

The NM_000767.5(CYP2B6):c.1459C>A (p.Arg487Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000713 (AC=115) in the gnomAD database across 1,613,602 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0013. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: CYP2B6 NM_000767.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• Publications: 2 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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -6 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).
	BS2Observed in healthy adult		Pure AD gene with cumulative gnomAD AC ≥5 — observed in healthy adults (BS2); GnomAD homozygous count = 0.; Very high cumulative gnomAD AC = 115 (any gene).

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.1459C>A p.Arg487Ser	missense	Exon 9 of 9	Prot: NP_000758.1 UniProt:

CYP2B6 NM_000767.5

MANE Select

HGVSc / HGVSpc.1459C>Ap.Arg487Ser

Exon rankExon 9 of 9

missense

Prot: NP_000758.1UniProt: P20813-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CYP2B6 ENST00000324071.10	TSL:1MANE Select	c.1459C>A p.Arg487Ser	missense	Exon 9 of 9	Prot: ENSP00000324648.2 UniProt:
	CYP2B6 ENST00000597612.1	TSL:1	n.812C>A	non_coding_transcript_exon	Exon 3 of 3	Prot:
	CYP2B6 ENST00000863358.1		c.1114C>A p.Arg372Ser	missense	Exon 7 of 7	Prot: ENSP00000533417.1 UniProt:

CYP2B6 ENST00000324071.10

TSL:1MANE Select

HGVSc / HGVSpc.1459C>Ap.Arg487Ser

Exon rankExon 9 of 9

missense

Prot: ENSP00000324648.2UniProt: P20813-1

CYP2B6 ENST00000597612.1

TSL:1

HGVSc / HGVSpn.812C>A

Exon rankExon 3 of 3

non_coding_transcript_exon

Prot:

CYP2B6 ENST00000863358.1

HGVSc / HGVSpc.1114C>Ap.Arg372Ser

Exon rankExon 7 of 7

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 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.000329	AC:50	Hom:0	AN:152096	Cov:31
GnomAD2 exomes	AF: 0.000120	AC:30	Hom:	AN:250440	Cov:
GnomAD4 exome	AF: 0.0000438	AC:64	Hom:0	AN:1461388	Cov:32
GnomAD4 genome	AF: 0.000335	AC:51	Hom:0	AN:152214	Cov:31
TOPMed (Bravo)	AF: 0.000416	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.0000356	AC:2	Hom:285	AN:56180	Cov:

Showing 6 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
Epi25(Epilepsy)	0.000143	6	41956	0.000135	9	66882
SCHEMA(Schizophrenia)	0.000246	29	117668	0.000303	61	201322

Showing 2 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	12
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.93
DANN	Benign	0.61
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.018	N
FuncVEP CTI	Benign	0.033
GPN-Star LLR	N/A	-4.3
GPN-Star score	N/A	4.3
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.0	T
Mutation Taster	N/A	82/18	polymorphism
MutationAssessor	Benign	0.39	N
PhyloP100	Benign	-0.85
popEVE	Benign	-2.4
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.027
Sift	Benign	0.48	T
Sift4G	Benign	0.57	T
Varity_R	N/A	0.46
VESM-3B	Benign	-5.7

Showing 28 of 28 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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.

Other links and lift over

dbSNP: rs3211371;

hg19: chr19-41522715;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar