chr19-40996697-G-A

Variant names:

• chr19-40996697-G-A
• rs6508964
• NM_000767.5:c.171+5221G>A

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+5221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,018 control chromosomes in the GnomAD database, including 38,518 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 0.70 (38518 hom., cov: 32)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 7 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 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+5221G>A		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+5221G>A		intron	N/A	ENSP00000324648.2
	CYP2B6	ENST00000598834.2	TSL:5	n.72+5221G>A		intron	N/A	ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105929 AN: 151900 Hom.: 38468 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.698 AC: 106038 AN: 152018 Hom.: 38518 Cov.: 32 AF XY: 0.700 AC XY: 51975 AN XY: 74302

African (AFR) AF: 0.901 AC: 37330 AN: 41454

American (AMR) AF: 0.758 AC: 11574 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2122 AN: 3466

East Asian (EAS) AF: 0.656 AC: 3394 AN: 5172

South Asian (SAS) AF: 0.754 AC: 3637 AN: 4826

European-Finnish (FIN) AF: 0.587 AC: 6186 AN: 10546

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

European-Non Finnish (NFE) AF: 0.585 AC: 39732 AN: 67970

Other (OTH) AF: 0.688 AC: 1452 AN: 2110

Alfa AF: 0.640 Hom.: 48422

Bravo AF: 0.717

Asia WGS AF: 0.714 AC: 2481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.93
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: rs6508964; hg19: chr19-41502602;