19-41009797-T-C

Variant names:

• chr19-41009797-T-C
• rs2279345
• ENST00000597612.1:n.121T>C

Variant summary

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

The ENST00000597612.1(CYP2B6):​n.121T>C 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 0.66 in 638,240 control chromosomes in the GnomAD database, including 141,372 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 0.68 (35360 hom., cov: 30)
  • Exomes 𝑓: 0.66 (106012 hom.)
• Consequence: CYP2B6 ENST00000597612.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 56 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.823-197T>C		intron_variant	Intron 5 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000597612.1	n.121T>C		non_coding_transcript_exon_variant	Exon 1 of 3	1
CYP2B6	ENST00000324071.10	c.823-197T>C		intron_variant	Intron 5 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000593831.1	c.257-2501T>C		intron_variant	Intron 2 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*264-197T>C		intron_variant	Intron 6 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102878 AN: 151798 Hom.: 35333 Cov.: 30

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.655 AC: 318542 AN: 486324 Hom.: 106012 Cov.: 5 AF XY: 0.663 AC XY: 170892 AN XY: 257874

African (AFR) AF: 0.748 AC: 10277 AN: 13734

American (AMR) AF: 0.826 AC: 20991 AN: 25412

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 10415 AN: 15194

East Asian (EAS) AF: 0.677 AC: 21051 AN: 31080

South Asian (SAS) AF: 0.790 AC: 38847 AN: 49160

European-Finnish (FIN) AF: 0.596 AC: 18509 AN: 31036

Middle Eastern (MID) AF: 0.778 AC: 2449 AN: 3148

European-Non Finnish (NFE) AF: 0.614 AC: 178047 AN: 290174

Other (OTH) AF: 0.656 AC: 17956 AN: 27386

GnomAD4 genome AF: 0.678 AC: 102955 AN: 151916 Hom.: 35360 Cov.: 30 AF XY: 0.683 AC XY: 50713 AN XY: 74248

African (AFR) AF: 0.750 AC: 31076 AN: 41458

American (AMR) AF: 0.786 AC: 11996 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2364 AN: 3468

East Asian (EAS) AF: 0.698 AC: 3582 AN: 5132

South Asian (SAS) AF: 0.782 AC: 3769 AN: 4818

European-Finnish (FIN) AF: 0.606 AC: 6386 AN: 10544

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41557 AN: 67908

Other (OTH) AF: 0.696 AC: 1472 AN: 2114

Alfa AF: 0.643 Hom.: 94215

Bravo AF: 0.691

Asia WGS AF: 0.727 AC: 2526 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	0.66
DANN	Benign	0.21
PhyloP100		-1.1
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: rs2279345; hg19: chr19-41515702;