19-40994688-C-T

Variant names:

• chr19-40994688-C-T
• rs4803415
• NM_000767.5:c.171+3212C>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.171+3212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 151,992 control chromosomes in the GnomAD database, including 878 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 0.093 (878 hom., cov: 32)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.05
• Publications: 5 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=-1.11).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.171+3212C>T		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.171+3212C>T		intron_variant	Intron 1 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000598834.2	n.72+3212C>T		intron_variant	Intron 1 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14137 AN: 151876 Hom.: 873 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.0924

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

GnomAD4 genome AF: 0.0931 AC: 14147 AN: 151992 Hom.: 878 Cov.: 32 AF XY: 0.0980 AC XY: 7283 AN XY: 74284

African (AFR) AF: 0.0420 AC: 1738 AN: 41410

American (AMR) AF: 0.153 AC: 2335 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 304 AN: 3472

East Asian (EAS) AF: 0.171 AC: 886 AN: 5178

South Asian (SAS) AF: 0.137 AC: 661 AN: 4814

European-Finnish (FIN) AF: 0.151 AC: 1597 AN: 10564

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0937 AC: 6368 AN: 67966

Other (OTH) AF: 0.0905 AC: 191 AN: 2110

Alfa AF: 0.0933 Hom.: 1151

Bravo AF: 0.0918

Asia WGS AF: 0.143 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.20
DANN	Benign	0.65
PhyloP100		-4.0
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: rs4803415; hg19: chr19-41500593;