chr19-41015733-G-A

Variant names:

• chr19-41015733-G-A
• rs7260329
• NM_000767.5:c.1295-913G>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.1295-913G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 150,932 control chromosomes in the GnomAD database, including 6,656 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 0.28 (6656 hom., cov: 29)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 37 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 (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.1295-913G>A		intron_variant	Intron 8 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.1295-913G>A		intron_variant	Intron 8 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1	n.648-913G>A		intron_variant	Intron 2 of 2	1
CYP2B6	ENST00000593831.1	c.587-913G>A		intron_variant	Intron 4 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*652-913G>A		intron_variant	Intron 9 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42497 AN: 150814 Hom.: 6653 Cov.: 29

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.282 AC: 42517 AN: 150932 Hom.: 6656 Cov.: 29 AF XY: 0.287 AC XY: 21109 AN XY: 73588

African (AFR) AF: 0.148 AC: 6092 AN: 41278

American (AMR) AF: 0.362 AC: 5478 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1128 AN: 3464

East Asian (EAS) AF: 0.429 AC: 2172 AN: 5060

South Asian (SAS) AF: 0.360 AC: 1700 AN: 4720

European-Finnish (FIN) AF: 0.357 AC: 3689 AN: 10346

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21269 AN: 67644

Other (OTH) AF: 0.292 AC: 613 AN: 2096

Alfa AF: 0.309 Hom.: 22491

Bravo AF: 0.281

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.59
PhyloP100		1.1
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: rs7260329; hg19: chr19-41521638;