rs1042389

Positions:

• chr19-41018248-T-C

Variant summary

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

The NM_000767.5(CYP2B6):​c.*1421T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,296 control chromosomes in the GnomAD database, including 3,551 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 0.21 (3544 hom., cov: 32)
  • Exomes 𝑓: 0.30 (7 hom.)
• Consequence: CYP2B6 NM_000767.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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 (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5	c.*1421T>C		3_prime_UTR_variant	9/9	ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10	c.*1421T>C		3_prime_UTR_variant	9/9	1	NM_000767.5	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32682 AN: 152052 Hom.: 3546 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.302 AC: 38 AN: 126 Hom.: 7 Cov.: 0 AF XY: 0.244 AC XY: 20 AN XY: 82

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.0962

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.215 AC: 32705 AN: 152170 Hom.: 3544 Cov.: 32 AF XY: 0.216 AC XY: 16089 AN XY: 74382

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.215

Alfa AF: 0.209 Hom.: 4127

Bravo AF: 0.211

Asia WGS AF: 0.248 AC: 862 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	2.2
DANN	Benign	0.50

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: rs1042389; hg19: chr19-41524153;