19-41004222-A-T

Variant names:

• chr19-41004222-A-T
• rs2279342
• NM_000767.5:c.334+59A>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.334+59A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,609,982 control chromosomes in the GnomAD database, including 9,825 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 0.097 (942 hom., cov: 30)
  • Exomes 𝑓: 0.10 (8883 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 16 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 = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.334+59A>T		intron_variant	Intron 2 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.334+59A>T		intron_variant	Intron 2 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000593831.1	c.106+59A>T		intron_variant	Intron 1 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.235+59A>T		intron_variant	Intron 2 of 9	5		ENSP00000496294.1
CYP2B6	ENST00000594187.1	n.-157A>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14650 AN: 151256 Hom.: 939 Cov.: 30

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0993

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.0966

GnomAD4 exome AF: 0.102 AC: 148587 AN: 1458608 Hom.: 8883 Cov.: 32 AF XY: 0.104 AC XY: 75174 AN XY: 725760

African (AFR) AF: 0.0416 AC: 1389 AN: 33410

American (AMR) AF: 0.235 AC: 10507 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2681 AN: 26112

East Asian (EAS) AF: 0.187 AC: 7432 AN: 39682

South Asian (SAS) AF: 0.141 AC: 12134 AN: 86116

European-Finnish (FIN) AF: 0.156 AC: 8325 AN: 53370

Middle Eastern (MID) AF: 0.138 AC: 793 AN: 5766

European-Non Finnish (NFE) AF: 0.0892 AC: 98940 AN: 1109232

Other (OTH) AF: 0.106 AC: 6386 AN: 60268

GnomAD4 genome AF: 0.0968 AC: 14657 AN: 151374 Hom.: 942 Cov.: 30 AF XY: 0.102 AC XY: 7516 AN XY: 73860

African (AFR) AF: 0.0417 AC: 1722 AN: 41302

American (AMR) AF: 0.160 AC: 2414 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.0993 AC: 344 AN: 3464

East Asian (EAS) AF: 0.174 AC: 886 AN: 5088

South Asian (SAS) AF: 0.141 AC: 673 AN: 4788

European-Finnish (FIN) AF: 0.154 AC: 1603 AN: 10414

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0992 AC: 6738 AN: 67896

Other (OTH) AF: 0.0947 AC: 199 AN: 2102

Alfa AF: 0.0586 Hom.: 80

Bravo AF: 0.0964

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.64
PhyloP100		-0.19
PromoterAI		0.017	Neutral
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: rs2279342; hg19: chr19-41510127; COSMIC: COSV57842913; COSMIC: COSV57842913;