rs2291287

Variant names:

• chr19-41016546-A-G
• rs2291287
• NM_000767.5:c.1295-100A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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 rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.1295-100A>G		intron_variant	Intron 8 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.1295-100A>G		intron_variant	Intron 8 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1	n.648-100A>G		intron_variant	Intron 2 of 2	1
CYP2B6	ENST00000593831.1	c.587-100A>G		intron_variant	Intron 4 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*652-100A>G		intron_variant	Intron 9 of 9	5		ENSP00000496294.1

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

African (AFR) AF: 0.0443 AC: 1190 AN: 26866

American (AMR) AF: 0.0324 AC: 1329 AN: 41046

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 1879 AN: 23762

East Asian (EAS) AF: 0.0520 AC: 1928 AN: 37042

South Asian (SAS) AF: 0.0340 AC: 2609 AN: 76746

European-Finnish (FIN) AF: 0.0488 AC: 2371 AN: 48570

Middle Eastern (MID) AF: 0.0953 AC: 459 AN: 4814

European-Non Finnish (NFE) AF: 0.0481 AC: 39530 AN: 822316

Other (OTH) AF: 0.0536 AC: 2651 AN: 49456

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

African (AFR) AF: 0.0427 AC: 1768 AN: 41434

American (AMR) AF: 0.0502 AC: 768 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3468

East Asian (EAS) AF: 0.0554 AC: 287 AN: 5180

South Asian (SAS) AF: 0.0401 AC: 193 AN: 4810

European-Finnish (FIN) AF: 0.0500 AC: 527 AN: 10534

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0531 AC: 3612 AN: 68012

Other (OTH) AF: 0.0623 AC: 131 AN: 2102

Alfa AF: 0.0527 Hom.: 383

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
PhyloP100		0.37
Mutation Taster		=100/0	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: rs2291287; hg19: chr19-41522451;