chr19-41017111-C-T

Variant names:

• chr19-41017111-C-T
• rs3181842
• ENST00000597612.1:n.1113C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000597612.1(CYP2B6):​n.1113C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 212,720 control chromosomes in the GnomAD database, including 47,826 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 0.66 (33508 hom., cov: 30)
  • Exomes 𝑓: 0.68 (14318 hom.)
• Consequence: CYP2B6 ENST00000597612.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.*284C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000597612.1	n.1113C>T		non_coding_transcript_exon_variant	Exon 3 of 3	1
CYP2B6	ENST00000324071.10	c.*284C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000593831.1	c.*284C>T		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*1117C>T		downstream_gene_variant		5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100239 AN: 151642 Hom.: 33465 Cov.: 30

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.684

GnomAD4 exome AF: 0.681 AC: 41533 AN: 60962 Hom.: 14318 Cov.: 2 AF XY: 0.691 AC XY: 21922 AN XY: 31718

African (AFR) AF: 0.728 AC: 1362 AN: 1872

American (AMR) AF: 0.791 AC: 3063 AN: 3870

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 1499 AN: 2046

East Asian (EAS) AF: 0.668 AC: 3057 AN: 4574

South Asian (SAS) AF: 0.811 AC: 4929 AN: 6080

European-Finnish (FIN) AF: 0.668 AC: 1303 AN: 1950

Middle Eastern (MID) AF: 0.798 AC: 225 AN: 282

European-Non Finnish (NFE) AF: 0.646 AC: 23636 AN: 36578

Other (OTH) AF: 0.663 AC: 2459 AN: 3710

GnomAD4 genome AF: 0.661 AC: 100335 AN: 151758 Hom.: 33508 Cov.: 30 AF XY: 0.668 AC XY: 49527 AN XY: 74172

African (AFR) AF: 0.714 AC: 29481 AN: 41310

American (AMR) AF: 0.773 AC: 11797 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2366 AN: 3466

East Asian (EAS) AF: 0.690 AC: 3556 AN: 5154

South Asian (SAS) AF: 0.782 AC: 3756 AN: 4802

European-Finnish (FIN) AF: 0.603 AC: 6354 AN: 10532

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40839 AN: 67916

Other (OTH) AF: 0.685 AC: 1443 AN: 2106

Alfa AF: 0.632 Hom.: 3791

Bravo AF: 0.672

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.39
PhyloP100		-2.7
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: rs3181842; hg19: chr19-41523016;