rs10403955

Variant names:

• chr19-41003533-T-G
• rs10403955
• NM_000767.5:c.172-468T>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.172-468T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,074 control chromosomes in the GnomAD database, including 7,212 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 0.30 (7212 hom., cov: 32)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 13 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000767.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	NM_000767.5	MANE Select	c.172-468T>G		intron	N/A	NP_000758.1	P20813-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	ENST00000324071.10	TSL:1 MANE Select	c.172-468T>G		intron	N/A	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000863358.1		c.172-3404T>G		intron	N/A	ENSP00000533417.1
	CYP2B6	ENST00000863357.1		c.172-5686T>G		intron	N/A	ENSP00000533416.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45412 AN: 151956 Hom.: 7211 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.299 AC: 45430 AN: 152074 Hom.: 7212 Cov.: 32 AF XY: 0.298 AC XY: 22133 AN XY: 74346

African (AFR) AF: 0.373 AC: 15454 AN: 41422

American (AMR) AF: 0.347 AC: 5308 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 981 AN: 3472

East Asian (EAS) AF: 0.205 AC: 1065 AN: 5188

South Asian (SAS) AF: 0.389 AC: 1875 AN: 4826

European-Finnish (FIN) AF: 0.216 AC: 2289 AN: 10580

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

European-Non Finnish (NFE) AF: 0.259 AC: 17624 AN: 67986

Other (OTH) AF: 0.307 AC: 650 AN: 2114

Alfa AF: 0.284 Hom.: 1027

Bravo AF: 0.307

Asia WGS AF: 0.320 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.84
PhyloP100		-0.0020
PromoterAI		-0.0050	Neutral
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: rs10403955; hg19: chr19-41509438;