19-41004222-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-41004222-A-T is Benign according to our data. Variant chr19-41004222-A-T is described in Lovd as [Likely_benign].
• 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/exons	MANE	UniProt
CYP2B6	NM_000767.5	c.334+59A>T		intron_variant		ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10	c.334+59A>T		intron_variant		1	NM_000767.5	P1
CYP2B6	ENST00000593831.1	c.106+59A>T		intron_variant		2
CYP2B6	ENST00000598834.2	c.236+59A>T		intron_variant, NMD_transcript_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

Gnomad4 AFR exome AF: 0.0416

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.0892

Gnomad4 OTH exome AF: 0.106

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

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0993

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.0947

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2279342; hg19: chr19-41510127; COSMIC: COSV57842913; COSMIC: COSV57842913;