19-41004045-G-C

Variant names:

• chr19-41004045-G-C
• rs2279341
• NM_000767.5:c.216G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000767.5(CYP2B6):​c.216G>C​(p.Pro72Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 1,613,632 control chromosomes in the GnomAD database, including 2,119 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.052 (253 hom., cov: 31)
  • Exomes 𝑓: 0.048 (1866 hom.)
• Consequence: CYP2B6 NM_000767.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.48
• Publications: 25 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-6.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	NM_000767.5	MANE Select	c.216G>C	p.Pro72Pro	synonymous	Exon 2 of 9	NP_000758.1	P20813-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	ENST00000324071.10	TSL:1 MANE Select	c.216G>C	p.Pro72Pro	synonymous	Exon 2 of 9	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000593831.1	TSL:2	c.-13G>C		5_prime_UTR	Exon 1 of 5	ENSP00000470582.1	M0QZJ2
	CYP2B6	ENST00000863358.1		c.172-2892G>C		intron	N/A	ENSP00000533417.1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7859 AN: 152062 Hom.: 252 Cov.: 31

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.0636

GnomAD2 exomes AF: 0.0490 AC: 12319 AN: 251244 AF XY: 0.0492

Gnomad AFR exome AF: 0.0448

Gnomad AMR exome AF: 0.0321

Gnomad ASJ exome AF: 0.0801

Gnomad EAS exome AF: 0.0456

Gnomad FIN exome AF: 0.0487

Gnomad NFE exome AF: 0.0565

Gnomad OTH exome AF: 0.0549

GnomAD4 exome AF: 0.0483 AC: 70595 AN: 1461452 Hom.: 1866 Cov.: 32 AF XY: 0.0484 AC XY: 35216 AN XY: 727060

African (AFR) AF: 0.0466 AC: 1560 AN: 33444

American (AMR) AF: 0.0324 AC: 1447 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 2139 AN: 26136

East Asian (EAS) AF: 0.0475 AC: 1886 AN: 39696

South Asian (SAS) AF: 0.0330 AC: 2849 AN: 86246

European-Finnish (FIN) AF: 0.0489 AC: 2612 AN: 53418

Middle Eastern (MID) AF: 0.0999 AC: 576 AN: 5768

European-Non Finnish (NFE) AF: 0.0488 AC: 54256 AN: 1111638

Other (OTH) AF: 0.0542 AC: 3270 AN: 60382

GnomAD4 genome AF: 0.0517 AC: 7874 AN: 152180 Hom.: 253 Cov.: 31 AF XY: 0.0519 AC XY: 3864 AN XY: 74400

African (AFR) AF: 0.0442 AC: 1835 AN: 41480

American (AMR) AF: 0.0513 AC: 784 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 307 AN: 3472

East Asian (EAS) AF: 0.0489 AC: 253 AN: 5174

South Asian (SAS) AF: 0.0388 AC: 187 AN: 4822

European-Finnish (FIN) AF: 0.0496 AC: 527 AN: 10624

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0539 AC: 3665 AN: 68014

Other (OTH) AF: 0.0630 AC: 133 AN: 2112

Alfa AF: 0.0592 Hom.: 101

Bravo AF: 0.0503

Asia WGS AF: 0.0440 AC: 152 AN: 3478

EpiCase AF: 0.0529

EpiControl AF: 0.0579

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.44
PhyloP100		-6.5
PromoterAI		-0.0039	Neutral
Mutation Taster		=295/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2279341; hg19: chr19-41509950;