rs8192718

Positions:

• chr19-41009909-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000767.5(CYP2B6):​c.823-85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,570,734 control chromosomes in the GnomAD database, including 222 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 0.012 (22 hom., cov: 31)
  • Exomes 𝑓: 0.013 (200 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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=-0.91).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0115 (1756/152272) while in subpopulation EAS AF= 0.0481 (249/5180). AF 95% confidence interval is 0.0432. There are 22 homozygotes in gnomad4. There are 874 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1756 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5	c.823-85G>A		intron_variant		ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10	c.823-85G>A		intron_variant		1	NM_000767.5	P1
CYP2B6	ENST00000597612.1	n.233G>A		non_coding_transcript_exon_variant	1/3	1
CYP2B6	ENST00000593831.1	c.257-2389G>A		intron_variant		2
CYP2B6	ENST00000598834.2	c.*264-85G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1754 AN: 152154 Hom.: 22 Cov.: 31

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.0128 AC: 18213 AN: 1418462 Hom.: 200 Cov.: 25 AF XY: 0.0134 AC XY: 9493 AN XY: 707634

Gnomad4 AFR exome AF: 0.00156

Gnomad4 AMR exome AF: 0.00779

Gnomad4 ASJ exome AF: 0.00509

Gnomad4 EAS exome AF: 0.0327

Gnomad4 SAS exome AF: 0.0259

Gnomad4 FIN exome AF: 0.0107

Gnomad4 NFE exome AF: 0.0117

Gnomad4 OTH exome AF: 0.0158

GnomAD4 genome AF: 0.0115 AC: 1756 AN: 152272 Hom.: 22 Cov.: 31 AF XY: 0.0117 AC XY: 874 AN XY: 74466

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.0481

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0131 Hom.: 26

Bravo AF: 0.0108

Asia WGS AF: 0.0320 AC: 112 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.52

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: rs8192718; hg19: chr19-41515814;