rs4803419

Variant names:

• chr19-41006887-C-T
• rs4803419
• NM_000767.5:c.485-18C>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.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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 94 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=-0.84).
• 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 rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.485-18C>T		intron_variant	Intron 3 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.485-18C>T		intron_variant	Intron 3 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000593831.1	c.256+2441C>T		intron_variant	Intron 2 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000594187.1	n.69-18C>T		intron_variant	Intron 1 of 1	5
CYP2B6	ENST00000598834.2	n.386-18C>T		intron_variant	Intron 3 of 9	5		ENSP00000496294.1

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

GnomAD2 exomes AF: 0.338 AC: 84067 AN: 248742 AF XY: 0.336

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 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

African (AFR) AF: 0.105 AC: 3494 AN: 33416

American (AMR) AF: 0.461 AC: 20485 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 8229 AN: 26104

East Asian (EAS) AF: 0.452 AC: 17937 AN: 39648

South Asian (SAS) AF: 0.352 AC: 30286 AN: 86020

European-Finnish (FIN) AF: 0.361 AC: 19237 AN: 53252

Middle Eastern (MID) AF: 0.367 AC: 1770 AN: 4826

European-Non Finnish (NFE) AF: 0.300 AC: 333278 AN: 1109348

Other (OTH) AF: 0.302 AC: 18195 AN: 60150

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

African (AFR) AF: 0.112 AC: 4638 AN: 41418

American (AMR) AF: 0.354 AC: 5413 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3468

East Asian (EAS) AF: 0.445 AC: 2301 AN: 5166

South Asian (SAS) AF: 0.347 AC: 1668 AN: 4808

European-Finnish (FIN) AF: 0.374 AC: 3956 AN: 10566

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21202 AN: 67950

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.295 Hom.: 10703

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
PhyloP100		-0.078
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: rs4803419; hg19: chr19-41512792;