19-41011783-T-C

Variant names:

• chr19-41011783-T-C
• rs6508965
• NM_000767.5:c.965-515T>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.965-515T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 151,742 control chromosomes in the GnomAD database, including 35,273 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 (35273 hom., cov: 29)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72
• Publications: 8 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.774 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.965-515T>C		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.965-515T>C		intron	N/A	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000597612.1	TSL:1	n.460-515T>C		intron	N/A
	CYP2B6	ENST00000863358.1		c.620-515T>C		intron	N/A	ENSP00000533417.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102651 AN: 151624 Hom.: 35248 Cov.: 29

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.677 AC: 102726 AN: 151742 Hom.: 35273 Cov.: 29 AF XY: 0.682 AC XY: 50577 AN XY: 74126

African (AFR) AF: 0.749 AC: 30945 AN: 41322

American (AMR) AF: 0.785 AC: 11974 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2365 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3593 AN: 5156

South Asian (SAS) AF: 0.784 AC: 3777 AN: 4820

European-Finnish (FIN) AF: 0.603 AC: 6338 AN: 10514

Middle Eastern (MID) AF: 0.822 AC: 240 AN: 292

European-Non Finnish (NFE) AF: 0.611 AC: 41514 AN: 67910

Other (OTH) AF: 0.697 AC: 1474 AN: 2114

Alfa AF: 0.645 Hom.: 86694

Bravo AF: 0.690

Asia WGS AF: 0.728 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.089
DANN	Benign	0.52
PhyloP100		-2.7
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: rs6508965; hg19: chr19-41517688;