rs2279344

Variant names:

• chr19-41009578-G-A
• rs2279344
• NM_000767.5:c.822+183G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):​c.822+183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 679,622 control chromosomes in the GnomAD database, including 150,721 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 0.70 (38033 hom., cov: 26)
  • Exomes 𝑓: 0.65 (112688 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.822+183G>A		intron_variant	Intron 5 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.822+183G>A		intron_variant	Intron 5 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000593831.1	c.257-2720G>A		intron_variant	Intron 2 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*263+183G>A		intron_variant	Intron 6 of 9	5		ENSP00000496294.1
CYP2B6	ENST00000597612.1	n.-99G>A		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 105901 AN: 150876 Hom.: 37981 Cov.: 26

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.718

GnomAD4 exome AF: 0.646 AC: 341264 AN: 528626 Hom.: 112688 Cov.: 6 AF XY: 0.654 AC XY: 180942 AN XY: 276826

African (AFR) AF: 0.839 AC: 11467 AN: 13664

American (AMR) AF: 0.818 AC: 16576 AN: 20252

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 9999 AN: 14568

East Asian (EAS) AF: 0.677 AC: 21289 AN: 31436

South Asian (SAS) AF: 0.790 AC: 36908 AN: 46704

European-Finnish (FIN) AF: 0.596 AC: 24506 AN: 41124

Middle Eastern (MID) AF: 0.784 AC: 1739 AN: 2218

European-Non Finnish (NFE) AF: 0.606 AC: 200030 AN: 330170

Other (OTH) AF: 0.658 AC: 18750 AN: 28490

GnomAD4 genome AF: 0.702 AC: 106010 AN: 150996 Hom.: 38033 Cov.: 26 AF XY: 0.707 AC XY: 52093 AN XY: 73684

African (AFR) AF: 0.834 AC: 34313 AN: 41120

American (AMR) AF: 0.794 AC: 12040 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2363 AN: 3464

East Asian (EAS) AF: 0.699 AC: 3538 AN: 5064

South Asian (SAS) AF: 0.781 AC: 3712 AN: 4754

European-Finnish (FIN) AF: 0.603 AC: 6289 AN: 10426

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41496 AN: 67696

Other (OTH) AF: 0.718 AC: 1508 AN: 2100

Alfa AF: 0.649 Hom.: 46643

Bravo AF: 0.719

Asia WGS AF: 0.738 AC: 2567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		-0.65
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: rs2279344; hg19: chr19-41515483;