chr19-41013663-T-C

Variant names:

• chr19-41013663-T-C
• rs33967301
• NM_000767.5:c.1294+848T>C

Variant summary

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

The NM_000767.5(CYP2B6):​c.1294+848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 152,282 control chromosomes in the GnomAD database, including 245 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 0.054 (245 hom., cov: 32)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.1294+848T>C		intron_variant	Intron 8 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.1294+848T>C		intron_variant	Intron 8 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1	n.647+1178T>C		intron_variant	Intron 2 of 2	1
CYP2B6	ENST00000593831.1	c.586+848T>C		intron_variant	Intron 4 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*651+633T>C		intron_variant	Intron 9 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8188 AN: 152164 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0539 AC: 8201 AN: 152282 Hom.: 245 Cov.: 32 AF XY: 0.0541 AC XY: 4027 AN XY: 74460

African (AFR) AF: 0.0527 AC: 2191 AN: 41560

American (AMR) AF: 0.0508 AC: 777 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.0550 AC: 285 AN: 5186

South Asian (SAS) AF: 0.0396 AC: 191 AN: 4826

European-Finnish (FIN) AF: 0.0494 AC: 524 AN: 10598

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0531 AC: 3613 AN: 68018

Other (OTH) AF: 0.0629 AC: 133 AN: 2114

Alfa AF: 0.0568 Hom.: 39

Bravo AF: 0.0529

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.62
PhyloP100		-0.083
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: rs33967301; hg19: chr19-41519568;