19-41012868-C-T

Variant summary

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

The NM_000767.5(CYP2B6):c.1294+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,599,590 control chromosomes in the GnomAD database, including 56,517 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 0.29 (6695 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49822 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47

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).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5	c.1294+53C>T		intron_variant		ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10	c.1294+53C>T		intron_variant		1	NM_000767.5	P1
CYP2B6	ENST00000597612.1	n.647+383C>T		intron_variant, non_coding_transcript_variant		1
CYP2B6	ENST00000593831.1	c.586+53C>T		intron_variant		2
CYP2B6	ENST00000598834.2	c.*594-105C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43621 AN: 151746 Hom.: 6695 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.257 AC: 371755 AN: 1447726 Hom.: 49822 Cov.: 27 AF XY: 0.261 AC XY: 187923 AN XY: 721130

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.287 AC: 43638 AN: 151864 Hom.: 6695 Cov.: 32 AF XY: 0.287 AC XY: 21309 AN XY: 74240

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.302

Alfa AF: 0.261 Hom.: 7588

Bravo AF: 0.298

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.084
Dann	Benign	0.62

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: rs8192719; hg19: chr19-41518773; COSMIC: COSV57842894;