19-41004045-G-C

Position:

• chr19-41004045-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.216G>C	p.Pro72Pro	synonymous_variant	2/9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.216G>C	p.Pro72Pro	synonymous_variant	2/9	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000593831.1	c.-13G>C		5_prime_UTR_variant	1/5	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.117G>C		non_coding_transcript_exon_variant	2/10	5		ENSP00000496294.1

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

GnomAD3 exomes AF: 0.0490 AC: 12319 AN: 251244 Hom.: 345 AF XY: 0.0492 AC XY: 6685 AN XY: 135784

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 SAS exome AF: 0.0338

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

Gnomad4 AFR exome AF: 0.0466

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.0818

Gnomad4 EAS exome AF: 0.0475

Gnomad4 SAS exome AF: 0.0330

Gnomad4 FIN exome AF: 0.0489

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.0542

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

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0884

Gnomad4 EAS AF: 0.0489

Gnomad4 SAS AF: 0.0388

Gnomad4 FIN AF: 0.0496

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.0630

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs2279341; hg19: chr19-41509950;