19-40998172-C-T

Variant names:

• chr19-40998172-C-T
• rs16974799
• NM_000767.5:c.172-5829C>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.172-5829C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,860 control chromosomes in the GnomAD database, including 7,233 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 0.30 (7233 hom., cov: 31)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.388 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.172-5829C>T		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.172-5829C>T		intron	N/A	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000863358.1		c.171+6696C>T		intron	N/A	ENSP00000533417.1
	CYP2B6	ENST00000863357.1		c.171+6696C>T		intron	N/A	ENSP00000533416.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45141 AN: 151742 Hom.: 7230 Cov.: 31

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.297 AC: 45163 AN: 151860 Hom.: 7233 Cov.: 31 AF XY: 0.298 AC XY: 22086 AN XY: 74214

African (AFR) AF: 0.388 AC: 16028 AN: 41346

American (AMR) AF: 0.352 AC: 5372 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3466

East Asian (EAS) AF: 0.215 AC: 1109 AN: 5152

South Asian (SAS) AF: 0.403 AC: 1943 AN: 4818

European-Finnish (FIN) AF: 0.190 AC: 2013 AN: 10570

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16816 AN: 67944

Other (OTH) AF: 0.314 AC: 662 AN: 2110

Alfa AF: 0.266 Hom.: 9705

Bravo AF: 0.309

Asia WGS AF: 0.331 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.43
PhyloP100		0.21
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: rs16974799; hg19: chr19-41504077;