rs1042389

Variant names:

• chr19-41018248-T-C
• rs1042389
• NM_000767.5:c.*1421T>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.*1421T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,296 control chromosomes in the GnomAD database, including 3,551 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 0.21 (3544 hom., cov: 32)
  • Exomes 𝑓: 0.30 (7 hom.)
• Consequence: CYP2B6 NM_000767.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 28 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	NM_000767.5	MANE Select	c.*1421T>C		3_prime_UTR	Exon 9 of 9	NP_000758.1	P20813-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	ENST00000324071.10	TSL:1 MANE Select	c.*1421T>C		3_prime_UTR	Exon 9 of 9	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000863358.1		c.*1421T>C		3_prime_UTR	Exon 7 of 7	ENSP00000533417.1
	CYP2B6	ENST00000863357.1		c.*1421T>C		3_prime_UTR	Exon 6 of 6	ENSP00000533416.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32682 AN: 152052 Hom.: 3546 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.302 AC: 38 AN: 126 Hom.: 7 Cov.: 0 AF XY: 0.244 AC XY: 20 AN XY: 82

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.534 AC: 31 AN: 58

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0962 AC: 5 AN: 52

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.215 AC: 32705 AN: 152170 Hom.: 3544 Cov.: 32 AF XY: 0.216 AC XY: 16089 AN XY: 74382

African (AFR) AF: 0.225 AC: 9342 AN: 41506

American (AMR) AF: 0.165 AC: 2529 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3472

East Asian (EAS) AF: 0.309 AC: 1598 AN: 5178

South Asian (SAS) AF: 0.233 AC: 1125 AN: 4830

European-Finnish (FIN) AF: 0.221 AC: 2344 AN: 10592

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14353 AN: 67976

Other (OTH) AF: 0.215 AC: 453 AN: 2108

Alfa AF: 0.208 Hom.: 9479

Bravo AF: 0.211

Asia WGS AF: 0.248 AC: 862 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.50
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: rs1042389; hg19: chr19-41524153;