19-41009350-C-T

Variant names:

• chr19-41009350-C-T
• rs45482602
• NM_000767.5:c.777C>T

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.777C>T​(p.Ser259Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,580,934 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: CYP2B6 NM_000767.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.55
• Publications: 43 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=-0.75).
• BP6: Variant 19-41009350-C-T is Benign according to our data. Variant chr19-41009350-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3040512.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.55 with no splicing effect.
• BS2: High AC in GnomAd4 at 192 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.777C>T	p.Ser259Ser	synonymous	Exon 5 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.777C>T	p.Ser259Ser	synonymous	Exon 5 of 9	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000863358.1		c.432C>T	p.Ser144Ser	synonymous	Exon 3 of 7	ENSP00000533417.1
	CYP2B6	ENST00000863357.1		c.303C>T	p.Ser101Ser	synonymous	Exon 2 of 6	ENSP00000533416.1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 192 AN: 150650 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00454

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00193

GnomAD2 exomes AF: 0.000322 AC: 79 AN: 245372 AF XY: 0.000241

Gnomad AFR exome AF: 0.00439

Gnomad AMR exome AF: 0.000147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000360

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000136 AC: 194 AN: 1430166 Hom.: 1 Cov.: 33 AF XY: 0.000117 AC XY: 83 AN XY: 712156

African (AFR) AF: 0.00402 AC: 129 AN: 32092

American (AMR) AF: 0.000182 AC: 8 AN: 43996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25772

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39340

South Asian (SAS) AF: 0.0000477 AC: 4 AN: 83888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.0000258 AC: 28 AN: 1086936

Other (OTH) AF: 0.000405 AC: 24 AN: 59244

GnomAD4 genome AF: 0.00127 AC: 192 AN: 150768 Hom.: 0 Cov.: 27 AF XY: 0.00141 AC XY: 104 AN XY: 73586

African (AFR) AF: 0.00453 AC: 185 AN: 40870

American (AMR) AF: 0.0000664 AC: 1 AN: 15068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10448

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67804

Other (OTH) AF: 0.00191 AC: 4 AN: 2094

Alfa AF: 0.0000105 Hom.: 0

Bravo AF: 0.00139

ClinVar

ClinVar submissions

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	-0.75
CADD	Benign	0.29
DANN	Benign	0.49
PhyloP100		-3.6
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: rs45482602; hg19: chr19-41515255;