19-40997717-A-G

Variant names:

• chr19-40997717-A-G
• rs7250873
• NM_000767.5:c.171+6241A>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.171+6241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,904 control chromosomes in the GnomAD database, including 7,728 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 0.31 (7728 hom., cov: 31)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.409 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.171+6241A>G		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.171+6241A>G		intron	N/A	ENSP00000324648.2
	CYP2B6	ENST00000598834.2	TSL:5	n.72+6241A>G		intron	N/A	ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46359 AN: 151786 Hom.: 7726 Cov.: 31

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.305 AC: 46384 AN: 151904 Hom.: 7728 Cov.: 31 AF XY: 0.305 AC XY: 22663 AN XY: 74258

African (AFR) AF: 0.414 AC: 17110 AN: 41298

American (AMR) AF: 0.356 AC: 5443 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1007 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1119 AN: 5172

South Asian (SAS) AF: 0.403 AC: 1944 AN: 4824

European-Finnish (FIN) AF: 0.190 AC: 2004 AN: 10566

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16845 AN: 67980

Other (OTH) AF: 0.322 AC: 680 AN: 2110

Alfa AF: 0.263 Hom.: 702

Bravo AF: 0.318

Asia WGS AF: 0.334 AC: 1158 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	2.1
DANN	Benign	0.54
PhyloP100		-0.16
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: rs7250873; hg19: chr19-41503622;