19-41010277-C-T

Variant names:

• chr19-41010277-C-T
• rs2306606
• NM_000767.5:c.964+142C>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.964+142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 967,550 control chromosomes in the GnomAD database, including 35,555 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 0.30 (7279 hom., cov: 31)
  • Exomes 𝑓: 0.26 (28276 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.964+142C>T		intron_variant	Intron 6 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.964+142C>T		intron_variant	Intron 6 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1	n.459+142C>T		intron_variant	Intron 1 of 2	1
CYP2B6	ENST00000593831.1	c.257-2021C>T		intron_variant	Intron 2 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*405+142C>T		intron_variant	Intron 7 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45114 AN: 151908 Hom.: 7279 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.255 AC: 208244 AN: 815524 Hom.: 28276 AF XY: 0.260 AC XY: 108653 AN XY: 417512

African (AFR) AF: 0.413 AC: 8470 AN: 20490

American (AMR) AF: 0.316 AC: 9867 AN: 31238

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 4824 AN: 18260

East Asian (EAS) AF: 0.188 AC: 6366 AN: 33778

South Asian (SAS) AF: 0.385 AC: 23029 AN: 59836

European-Finnish (FIN) AF: 0.194 AC: 6663 AN: 34434

Middle Eastern (MID) AF: 0.287 AC: 802 AN: 2796

European-Non Finnish (NFE) AF: 0.240 AC: 138015 AN: 575906

Other (OTH) AF: 0.263 AC: 10208 AN: 38786

GnomAD4 genome AF: 0.297 AC: 45131 AN: 152026 Hom.: 7279 Cov.: 31 AF XY: 0.297 AC XY: 22036 AN XY: 74320

African (AFR) AF: 0.406 AC: 16809 AN: 41404

American (AMR) AF: 0.344 AC: 5266 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1070 AN: 5176

South Asian (SAS) AF: 0.377 AC: 1813 AN: 4812

European-Finnish (FIN) AF: 0.191 AC: 2016 AN: 10576

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16413 AN: 67978

Other (OTH) AF: 0.306 AC: 647 AN: 2116

Alfa AF: 0.156 Hom.: 309

Bravo AF: 0.309

Asia WGS AF: 0.319 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.33
PhyloP100		0.19
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: rs2306606; hg19: chr19-41516182; COSMIC: COSV57845978; COSMIC: COSV57845978;