rs11673270

Variant names:

• chr19-41014939-A-C
• rs11673270
• NM_000767.5:c.1295-1707A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-41014939-A-C
• chr19-41014939-A-G
• chr19-41014939-A-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.1295-1707A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,796 control chromosomes in the GnomAD database, including 8,517 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 0.32 (8517 hom., cov: 30)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	NM_000767.5	MANE Select	c.1295-1707A>C		intron	N/A	NP_000758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	ENST00000324071.10	TSL:1 MANE Select	c.1295-1707A>C		intron	N/A	ENSP00000324648.2
	CYP2B6	ENST00000597612.1	TSL:1	n.648-1707A>C		intron	N/A
	CYP2B6	ENST00000593831.1	TSL:2	c.587-1707A>C		intron	N/A	ENSP00000470582.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47867 AN: 151678 Hom.: 8503 Cov.: 30

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.316 AC: 47919 AN: 151796 Hom.: 8517 Cov.: 30 AF XY: 0.314 AC XY: 23307 AN XY: 74188

African (AFR) AF: 0.472 AC: 19503 AN: 41296

American (AMR) AF: 0.348 AC: 5302 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1064 AN: 5160

South Asian (SAS) AF: 0.378 AC: 1813 AN: 4802

European-Finnish (FIN) AF: 0.190 AC: 2013 AN: 10580

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

European-Non Finnish (NFE) AF: 0.242 AC: 16439 AN: 67950

Other (OTH) AF: 0.324 AC: 684 AN: 2110

Alfa AF: 0.254 Hom.: 6779

Bravo AF: 0.331

Asia WGS AF: 0.330 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.70
PhyloP100		-0.033
Mutation Taster		=98/2	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: rs11673270; hg19: chr19-41520844;