chr19-41013810-A-C

Variant names:

• chr19-41013810-A-C
• rs11671243
• NM_000767.5:c.1294+995A>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.1294+995A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,056 control chromosomes in the GnomAD database, including 35,432 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 0.68 (35432 hom., cov: 32)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• Publications: 7 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=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.1294+995A>C		intron_variant	Intron 8 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.1294+995A>C		intron_variant	Intron 8 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1	n.647+1325A>C		intron_variant	Intron 2 of 2	1
CYP2B6	ENST00000593831.1	c.586+995A>C		intron_variant	Intron 4 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*651+780A>C		intron_variant	Intron 9 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102993 AN: 151938 Hom.: 35407 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.678 AC: 103069 AN: 152056 Hom.: 35432 Cov.: 32 AF XY: 0.683 AC XY: 50760 AN XY: 74312

African (AFR) AF: 0.751 AC: 31157 AN: 41478

American (AMR) AF: 0.785 AC: 12004 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2367 AN: 3472

East Asian (EAS) AF: 0.696 AC: 3589 AN: 5160

South Asian (SAS) AF: 0.786 AC: 3786 AN: 4818

European-Finnish (FIN) AF: 0.603 AC: 6373 AN: 10570

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41565 AN: 67958

Other (OTH) AF: 0.698 AC: 1475 AN: 2114

Alfa AF: 0.516 Hom.: 1371

Bravo AF: 0.691

Asia WGS AF: 0.730 AC: 2538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.20
DANN	Benign	0.23
PhyloP100		-3.1
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: rs11671243; hg19: chr19-41519715;