19-41009202-C-T

Variant names:

• chr19-41009202-C-T
• rs12721646
• NM_000767.5:c.646-17C>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.646-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00996 in 1,607,186 control chromosomes in the GnomAD database, including 1,157 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 0.051 (618 hom., cov: 26)
  • Exomes 𝑓: 0.0057 (539 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 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.646-17C>T		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.646-17C>T		intron	N/A	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000863358.1		c.301-17C>T		intron	N/A	ENSP00000533417.1
	CYP2B6	ENST00000863357.1		c.172-17C>T		intron	N/A	ENSP00000533416.1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7689 AN: 150648 Hom.: 614 Cov.: 26

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.000884

Gnomad OTH AF: 0.0380

GnomAD2 exomes AF: 0.0136 AC: 3334 AN: 245904 AF XY: 0.00985

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.0119

Gnomad ASJ exome AF: 0.00453

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.00835

GnomAD4 exome AF: 0.00569 AC: 8291 AN: 1456422 Hom.: 539 Cov.: 32 AF XY: 0.00497 AC XY: 3604 AN XY: 724854

African (AFR) AF: 0.174 AC: 5777 AN: 33270

American (AMR) AF: 0.0133 AC: 594 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00525 AC: 137 AN: 26074

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.000360 AC: 31 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.0142 AC: 81 AN: 5702

European-Non Finnish (NFE) AF: 0.000717 AC: 794 AN: 1107286

Other (OTH) AF: 0.0145 AC: 876 AN: 60210

GnomAD4 genome AF: 0.0512 AC: 7719 AN: 150764 Hom.: 618 Cov.: 26 AF XY: 0.0496 AC XY: 3647 AN XY: 73562

African (AFR) AF: 0.175 AC: 7152 AN: 40754

American (AMR) AF: 0.0268 AC: 404 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00127 AC: 6 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10490

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.000884 AC: 60 AN: 67842

Other (OTH) AF: 0.0376 AC: 78 AN: 2076

Alfa AF: 0.00873 Hom.: 14

Bravo AF: 0.0597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.74
PhyloP100		0.20
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: rs12721646; hg19: chr19-41515107;