19-41018182-A-G

Variant summary

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

The NM_000767.5(CYP2B6):c.*1355A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 151,970 control chromosomes in the GnomAD database, including 36,107 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 0.68 (36107 hom., cov: 31)
  • Exomes 𝑓: 0.90 (21 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2B6 NM_000767.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5	c.*1355A>G		3_prime_UTR_variant	9/9	ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10	c.*1355A>G		3_prime_UTR_variant	9/9	1	NM_000767.5	P1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103731 AN: 151852 Hom.: 36079 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.701

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.896 AC: 43 AN: 48 Hom.: 21 Cov.: 0 AF XY: 0.833 AC XY: 20 AN XY: 24

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.722

GnomAD4 genome AF: 0.683 AC: 103809 AN: 151970 Hom.: 36107 Cov.: 31 AF XY: 0.688 AC XY: 51109 AN XY: 74254

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.702

Alfa AF: 0.623 Hom.: 22131

Bravo AF: 0.698

Asia WGS AF: 0.721 AC: 2506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.2
Dann	Benign	0.46

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: rs707265; hg19: chr19-41524087;