19-40992828-T-C

Variant names:

• chr19-40992828-T-C
• rs6508963
• NM_000767.5:c.171+1352T>C

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+1352T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,930 control chromosomes in the GnomAD database, including 7,763 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 (7763 hom., cov: 32)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.171+1352T>C		intron_variant	Intron 1 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.171+1352T>C		intron_variant	Intron 1 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000598834.2	n.72+1352T>C		intron_variant	Intron 1 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46823 AN: 151812 Hom.: 7759 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.308 AC: 46857 AN: 151930 Hom.: 7763 Cov.: 32 AF XY: 0.313 AC XY: 23243 AN XY: 74254

African (AFR) AF: 0.199 AC: 8239 AN: 41400

American (AMR) AF: 0.362 AC: 5527 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1119 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2269 AN: 5160

South Asian (SAS) AF: 0.348 AC: 1676 AN: 4810

European-Finnish (FIN) AF: 0.395 AC: 4173 AN: 10558

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.336 AC: 22825 AN: 67970

Other (OTH) AF: 0.308 AC: 651 AN: 2112

Alfa AF: 0.326 Hom.: 1403

Bravo AF: 0.304

Asia WGS AF: 0.361 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.85
PhyloP100		0.21
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: rs6508963; hg19: chr19-41498733;