19-41000286-T-C

Variant names:

• chr19-41000286-T-C
• rs3786547
• NM_000767.5:c.172-3715T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):​c.172-3715T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,078 control chromosomes in the GnomAD database, including 6,932 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 0.29 (6932 hom., cov: 32)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

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.172-3715T>C		intron	N/A	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.172-3715T>C		intron	N/A	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000863358.1		c.172-6651T>C		intron	N/A	ENSP00000533417.1
	CYP2B6	ENST00000863357.1		c.171+8810T>C		intron	N/A	ENSP00000533416.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43957 AN: 151960 Hom.: 6929 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.289 AC: 43975 AN: 152078 Hom.: 6932 Cov.: 32 AF XY: 0.289 AC XY: 21476 AN XY: 74346

African (AFR) AF: 0.385 AC: 15932 AN: 41410

American (AMR) AF: 0.343 AC: 5252 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3466

East Asian (EAS) AF: 0.213 AC: 1106 AN: 5184

South Asian (SAS) AF: 0.384 AC: 1850 AN: 4816

European-Finnish (FIN) AF: 0.182 AC: 1935 AN: 10608

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16096 AN: 67984

Other (OTH) AF: 0.305 AC: 644 AN: 2114

Alfa AF: 0.274 Hom.: 3388

Bravo AF: 0.301

Asia WGS AF: 0.323 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.83
PhyloP100		-1.0
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: rs3786547; hg19: chr19-41506191;