rs10500282

Variant names:

• chr19-41002537-T-C
• rs10500282
• NM_000767.5:c.172-1464T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-41002537-T-C
• chr19-41002537-T-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.172-1464T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,878 control chromosomes in the GnomAD database, including 7,717 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 0.31 (7717 hom., cov: 31)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.172-1464T>C		intron_variant	Intron 1 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.172-1464T>C		intron_variant	Intron 1 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000598834.2	n.73-1464T>C		intron_variant	Intron 1 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46654 AN: 151760 Hom.: 7715 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.310

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46670 AN: 151878 Hom.: 7717 Cov.: 31 AF XY: 0.306 AC XY: 22722 AN XY: 74220

African (AFR) AF: 0.406 AC: 16799 AN: 41356

American (AMR) AF: 0.350 AC: 5337 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1102 AN: 5178

South Asian (SAS) AF: 0.389 AC: 1869 AN: 4802

European-Finnish (FIN) AF: 0.212 AC: 2237 AN: 10576

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17469 AN: 67964

Other (OTH) AF: 0.313 AC: 657 AN: 2100

Alfa AF: 0.258 Hom.: 6222

Bravo AF: 0.318

Asia WGS AF: 0.325 AC: 1127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.68
DANN	Benign	0.54
PhyloP100		-1.4
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: rs10500282; hg19: chr19-41508442;