rs4803419

Positions:

• chr19-41006887-C-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.485-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,609,112 control chromosomes in the GnomAD database, including 79,698 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 0.27 (6503 hom., cov: 30)
  • Exomes 𝑓: 0.31 (73195 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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=-0.84).
• BP6: Variant 19-41006887-C-T is Benign according to our data. Variant chr19-41006887-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5	c.485-18C>T		intron_variant		ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10	c.485-18C>T		intron_variant		1	NM_000767.5	P1
CYP2B6	ENST00000593831.1	c.256+2441C>T		intron_variant		2
CYP2B6	ENST00000598834.2	c.387-18C>T		intron_variant, NMD_transcript_variant		5
CYP2B6	ENST00000594187.1	n.69-18C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41225 AN: 151840 Hom.: 6503 Cov.: 30

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.286

GnomAD3 exomes AF: 0.338 AC: 84067 AN: 248742 Hom.: 15133 AF XY: 0.336 AC XY: 45197 AN XY: 134366

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.475

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.447

Gnomad SAS exome AF: 0.347

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.311 AC: 452911 AN: 1457154 Hom.: 73195 Cov.: 33 AF XY: 0.313 AC XY: 226918 AN XY: 724898

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.461

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.352

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.271 AC: 41236 AN: 151958 Hom.: 6503 Cov.: 30 AF XY: 0.278 AC XY: 20655 AN XY: 74262

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.286

Alfa AF: 0.295 Hom.: 1339

Bravo AF: 0.265

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.80

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: rs4803419; hg19: chr19-41512792;