chr19-41014446-C-T

Variant names:

• chr19-41014446-C-T
• rs7255374
• NM_000767.5:c.1294+1631C>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.1294+1631C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,802 control chromosomes in the GnomAD database, including 9,116 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 0.34 (9116 hom., cov: 31)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 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.1294+1631C>T		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.1294+1631C>T		intron	N/A	ENSP00000324648.2
	CYP2B6	ENST00000597612.1	TSL:1	n.647+1961C>T		intron	N/A
	CYP2B6	ENST00000593831.1	TSL:2	c.586+1631C>T		intron	N/A	ENSP00000470582.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51399 AN: 151684 Hom.: 9115 Cov.: 31

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.339 AC: 51428 AN: 151802 Hom.: 9116 Cov.: 31 AF XY: 0.339 AC XY: 25104 AN XY: 74156

African (AFR) AF: 0.416 AC: 17210 AN: 41358

American (AMR) AF: 0.391 AC: 5961 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1358 AN: 5166

South Asian (SAS) AF: 0.418 AC: 2005 AN: 4800

European-Finnish (FIN) AF: 0.240 AC: 2528 AN: 10518

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20016 AN: 67938

Other (OTH) AF: 0.365 AC: 764 AN: 2094

Alfa AF: 0.323 Hom.: 910

Bravo AF: 0.347

Asia WGS AF: 0.365 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.25
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7255374; hg19: chr19-41520351;