rs7246456

Variant names:

• chr19-41012173-C-T
• rs7246456
• NM_000767.5:c.965-125C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):​c.965-125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 864,922 control chromosomes in the GnomAD database, including 32,235 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 (6678 hom., cov: 31)
  • Exomes 𝑓: 0.26 (25557 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.965-125C>T		intron_variant	Intron 6 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.965-125C>T		intron_variant	Intron 6 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1	n.460-125C>T		intron_variant	Intron 1 of 2	1
CYP2B6	ENST00000593831.1	c.257-125C>T		intron_variant	Intron 2 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*406-125C>T		intron_variant	Intron 7 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43529 AN: 151956 Hom.: 6677 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.261 AC: 185757 AN: 712846 Hom.: 25557 AF XY: 0.267 AC XY: 100138 AN XY: 375452

African (AFR) AF: 0.380 AC: 7018 AN: 18466

American (AMR) AF: 0.317 AC: 10961 AN: 34608

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 5487 AN: 20622

East Asian (EAS) AF: 0.189 AC: 6222 AN: 32874

South Asian (SAS) AF: 0.386 AC: 25306 AN: 65550

European-Finnish (FIN) AF: 0.195 AC: 7039 AN: 36122

Middle Eastern (MID) AF: 0.287 AC: 784 AN: 2734

European-Non Finnish (NFE) AF: 0.243 AC: 113522 AN: 466316

Other (OTH) AF: 0.265 AC: 9418 AN: 35554

GnomAD4 genome AF: 0.286 AC: 43546 AN: 152076 Hom.: 6678 Cov.: 31 AF XY: 0.286 AC XY: 21271 AN XY: 74368

African (AFR) AF: 0.369 AC: 15289 AN: 41470

American (AMR) AF: 0.342 AC: 5220 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1067 AN: 5154

South Asian (SAS) AF: 0.377 AC: 1820 AN: 4822

European-Finnish (FIN) AF: 0.190 AC: 2015 AN: 10590

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16407 AN: 67984

Other (OTH) AF: 0.300 AC: 632 AN: 2108

Alfa AF: 0.267 Hom.: 765

Bravo AF: 0.297

Asia WGS AF: 0.317 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.35
PhyloP100		-0.016
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: rs7246456; hg19: chr19-41518078;