rs150742423

Variant names:

• chr19-40991359-C-A
• rs150742423
• NM_000767.5:c.54C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_000767.5(CYP2B6):​c.54C>A​(p.Leu18Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000576 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00058 (0 hom.)
• Consequence: CYP2B6 NM_000767.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.63
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-40991359-C-A is Benign according to our data. Variant chr19-40991359-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3048896.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.63 with no splicing effect.
• BS2: High AC in GnomAd4 at 86 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000767.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	NM_000767.5	MANE Select	c.54C>A	p.Leu18Leu	synonymous	Exon 1 of 9	NP_000758.1	P20813-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	ENST00000324071.10	TSL:1 MANE Select	c.54C>A	p.Leu18Leu	synonymous	Exon 1 of 9	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000863358.1		c.54C>A	p.Leu18Leu	synonymous	Exon 1 of 7	ENSP00000533417.1
	CYP2B6	ENST00000863357.1		c.54C>A	p.Leu18Leu	synonymous	Exon 1 of 6	ENSP00000533416.1

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152114 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00491

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000705

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000577 AC: 145 AN: 251472 AF XY: 0.000537

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00486

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.000519

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.000577 AC: 843 AN: 1461748 Hom.: 0 Cov.: 31 AF XY: 0.000590 AC XY: 429 AN XY: 727172

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00482 AC: 126 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00122 AC: 65 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000529 AC: 588 AN: 1111880

Other (OTH) AF: 0.000911 AC: 55 AN: 60396

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152232 Hom.: 0 Cov.: 31 AF XY: 0.000618 AC XY: 46 AN XY: 74426

African (AFR) AF: 0.0000964 AC: 4 AN: 41500

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00491 AC: 17 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000930 Hom.: 1

Bravo AF: 0.000351

EpiCase AF: 0.000872

EpiControl AF: 0.000652

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CYP2B6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.40
PhyloP100		-1.6
PromoterAI		0.010	Neutral
Mutation Taster		=100/0	polymorphism

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: rs150742423; hg19: chr19-41497264;