chr19-41010277-C-A

Variant names:

• chr19-41010277-C-A
• rs2306606
• NM_000767.5:c.964+142C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000767.5(CYP2B6):​c.964+142C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000122 in 816,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.964+142C>A		intron_variant	Intron 6 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.964+142C>A		intron_variant	Intron 6 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1	n.459+142C>A		intron_variant	Intron 1 of 2	1
CYP2B6	ENST00000593831.1	c.257-2021C>A		intron_variant	Intron 2 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2	n.*405+142C>A		intron_variant	Intron 7 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000122 AC: 1 AN: 816898 Hom.: 0 AF XY: 0.00000239 AC XY: 1 AN XY: 418234

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20528

American (AMR) AF: 0.00 AC: 0 AN: 31278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18292

East Asian (EAS) AF: 0.00 AC: 0 AN: 33804

South Asian (SAS) AF: 0.0000167 AC: 1 AN: 59900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2804

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 577000

Other (OTH) AF: 0.00 AC: 0 AN: 38828

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.37
PhyloP100		0.19

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: rs2306606; hg19: chr19-41516182;