rs2291287

chr19-41016546-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):c.1295-100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,282,654 control chromosomes in the GnomAD database, including 1,684 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 0.051 (231 hom., cov: 31)
  • Exomes 𝑓: 0.048 (1453 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5	c.1295-100A>G		intron_variant		ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10	c.1295-100A>G		intron_variant		1	NM_000767.5	P1
CYP2B6	ENST00000597612.1	n.648-100A>G		intron_variant, non_coding_transcript_variant		1
CYP2B6	ENST00000593831.1	c.587-100A>G		intron_variant		2
CYP2B6	ENST00000598834.2	c.*652-100A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7760 AN: 151924 Hom.: 231 Cov.: 31

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0629

GnomAD4 exome AF: 0.0477 AC: 53946 AN: 1130618 Hom.: 1453 AF XY: 0.0480 AC XY: 27557 AN XY: 574682

Gnomad4 AFR exome AF: 0.0443

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.0791

Gnomad4 EAS exome AF: 0.0520

Gnomad4 SAS exome AF: 0.0340

Gnomad4 FIN exome AF: 0.0488

Gnomad4 NFE exome AF: 0.0481

Gnomad4 OTH exome AF: 0.0536

GnomAD4 genome AF: 0.0511 AC: 7773 AN: 152036 Hom.: 231 Cov.: 31 AF XY: 0.0514 AC XY: 3816 AN XY: 74280

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.0554

Gnomad4 SAS AF: 0.0401

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0531

Gnomad4 OTH AF: 0.0623

Alfa AF: 0.0533 Hom.: 316

Bravo AF: 0.0496

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.4
Dann	Benign	0.70

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: rs2291287; hg19: chr19-41522451;