rs4803418

chr19-41005898-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000767.5(CYP2B6):c.485-1007C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,798 control chromosomes in the GnomAD database, including 6,517 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 (6517 hom., cov: 31)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 19-41005898-C-G is Benign according to our data. Variant chr19-41005898-C-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5	c.485-1007C>G		intron_variant		ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10	c.485-1007C>G		intron_variant		1	NM_000767.5	P1
CYP2B6	ENST00000593831.1	c.256+1452C>G		intron_variant		2
CYP2B6	ENST00000598834.2	c.387-1007C>G		intron_variant, NMD_transcript_variant		5
CYP2B6	ENST00000594187.1	n.69-1007C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41579 AN: 151680 Hom.: 6517 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41596 AN: 151798 Hom.: 6517 Cov.: 31 AF XY: 0.281 AC XY: 20833 AN XY: 74184

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.286

Alfa AF: 0.292 Hom.: 883

Bravo AF: 0.267

Asia WGS AF: 0.352 AC: 1226 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	3.0
Dann	Benign	0.82

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: rs4803418; hg19: chr19-41511803;