19-41018182-A-G

Variant names:

• chr19-41018182-A-G
• rs707265
• NM_000767.5:c.*1355A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 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=-0.96).
• 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 rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.*1355A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.*1355A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_000767.5	ENSP00000324648.2

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 28 AN: 28

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.722 AC: 13 AN: 18

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.788 AC: 32647 AN: 41456

American (AMR) AF: 0.784 AC: 11972 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2405 AN: 3468

East Asian (EAS) AF: 0.663 AC: 3427 AN: 5170

South Asian (SAS) AF: 0.779 AC: 3747 AN: 4810

European-Finnish (FIN) AF: 0.598 AC: 6299 AN: 10526

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.605 AC: 41082 AN: 67956

Other (OTH) AF: 0.702 AC: 1482 AN: 2110

Alfa AF: 0.630 Hom.: 74215

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
PhyloP100		-0.25
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: rs707265; hg19: chr19-41524087;