rs7255374

Positions:

• chr19-41014446-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.1294+1631C>T		intron_variant		ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.1294+1631C>T		intron_variant		1	NM_000767.5	ENSP00000324648	P1
CYP2B6	ENST00000597612.1	n.647+1961C>T		intron_variant, non_coding_transcript_variant		1
CYP2B6	ENST00000593831.1	c.586+1631C>T		intron_variant		2		ENSP00000470582
CYP2B6	ENST00000598834.2	c.*651+1416C>T		intron_variant, NMD_transcript_variant		5		ENSP00000496294

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

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.365

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs7255374; hg19: chr19-41520351;