19-41012868-C-T

Variant names:

• chr19-41012868-C-T
• rs8192719
• NM_000767.5:c.1294+53C>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.1294+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,599,590 control chromosomes in the GnomAD database, including 56,517 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 (6695 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49822 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 61 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 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.1294+53C>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.1294+53C>T		intron	N/A	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000597612.1	TSL:1	n.647+383C>T		intron	N/A
	CYP2B6	ENST00000863358.1		c.949+53C>T		intron	N/A	ENSP00000533417.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43621 AN: 151746 Hom.: 6695 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.257 AC: 371755 AN: 1447726 Hom.: 49822 Cov.: 27 AF XY: 0.261 AC XY: 187923 AN XY: 721130

African (AFR) AF: 0.388 AC: 12828 AN: 33076

American (AMR) AF: 0.320 AC: 14288 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6970 AN: 26080

East Asian (EAS) AF: 0.191 AC: 7591 AN: 39646

South Asian (SAS) AF: 0.389 AC: 33437 AN: 85948

European-Finnish (FIN) AF: 0.196 AC: 10266 AN: 52314

Middle Eastern (MID) AF: 0.279 AC: 1604 AN: 5742

European-Non Finnish (NFE) AF: 0.244 AC: 268969 AN: 1100300

Other (OTH) AF: 0.264 AC: 15802 AN: 59944

GnomAD4 genome AF: 0.287 AC: 43638 AN: 151864 Hom.: 6695 Cov.: 32 AF XY: 0.287 AC XY: 21309 AN XY: 74240

African (AFR) AF: 0.373 AC: 15394 AN: 41318

American (AMR) AF: 0.341 AC: 5198 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 914 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1071 AN: 5160

South Asian (SAS) AF: 0.377 AC: 1818 AN: 4816

European-Finnish (FIN) AF: 0.191 AC: 2021 AN: 10584

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

European-Non Finnish (NFE) AF: 0.241 AC: 16399 AN: 67950

Other (OTH) AF: 0.302 AC: 638 AN: 2114

Alfa AF: 0.263 Hom.: 17961

Bravo AF: 0.298

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.084
DANN	Benign	0.62
PhyloP100		-2.5
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: rs8192719; hg19: chr19-41518773; COSMIC: COSV57842894;