rs4803417

Variant names:

• chr19-41002115-C-A
• rs4803417
• NM_000767.5:c.172-1886C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41002115-C-A
• chr19-41002115-C-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.172-1886C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,924 control chromosomes in the GnomAD database, including 34,809 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 0.67 (34809 hom., cov: 31)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.172-1886C>A		intron_variant	Intron 1 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.172-1886C>A		intron_variant	Intron 1 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000598834.2	n.73-1886C>A		intron_variant	Intron 1 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101505 AN: 151806 Hom.: 34764 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.669 AC: 101608 AN: 151924 Hom.: 34809 Cov.: 31 AF XY: 0.672 AC XY: 49877 AN XY: 74250

African (AFR) AF: 0.801 AC: 33168 AN: 41384

American (AMR) AF: 0.745 AC: 11378 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2124 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3390 AN: 5164

South Asian (SAS) AF: 0.754 AC: 3625 AN: 4810

European-Finnish (FIN) AF: 0.586 AC: 6181 AN: 10550

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39721 AN: 67950

Other (OTH) AF: 0.667 AC: 1407 AN: 2110

Alfa AF: 0.615 Hom.: 77083

Bravo AF: 0.684

Asia WGS AF: 0.709 AC: 2465 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.52
PhyloP100		0.19
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: rs4803417; hg19: chr19-41508020;