chr19-41009932-G-A

Variant names:

• chr19-41009932-G-A
• rs12721649
• NM_000767.5:c.823-62G>A

Variant summary

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

The NM_000767.5(CYP2B6):​c.823-62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,605,752 control chromosomes in the GnomAD database, including 1,298 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 0.054 (698 hom., cov: 31)
  • Exomes 𝑓: 0.0061 (600 hom.)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 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.823-62G>A		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.823-62G>A		intron	N/A	ENSP00000324648.2	P20813-1
	CYP2B6	ENST00000597612.1	TSL:1	n.256G>A		non_coding_transcript_exon	Exon 1 of 3
	CYP2B6	ENST00000863358.1		c.478-62G>A		intron	N/A	ENSP00000533417.1

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8209 AN: 152038 Hom.: 693 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000956

Gnomad OTH AF: 0.0397

GnomAD4 exome AF: 0.00605 AC: 8799 AN: 1453596 Hom.: 600 Cov.: 29 AF XY: 0.00532 AC XY: 3851 AN XY: 723550

African (AFR) AF: 0.182 AC: 6074 AN: 33324

American (AMR) AF: 0.0142 AC: 633 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00621 AC: 162 AN: 26080

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39646

South Asian (SAS) AF: 0.000885 AC: 76 AN: 85902

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51758

Middle Eastern (MID) AF: 0.0143 AC: 82 AN: 5750

European-Non Finnish (NFE) AF: 0.000759 AC: 840 AN: 1106430

Other (OTH) AF: 0.0155 AC: 929 AN: 60106

GnomAD4 genome AF: 0.0542 AC: 8243 AN: 152156 Hom.: 698 Cov.: 31 AF XY: 0.0525 AC XY: 3907 AN XY: 74394

African (AFR) AF: 0.184 AC: 7647 AN: 41458

American (AMR) AF: 0.0275 AC: 421 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000956 AC: 65 AN: 68004

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0201 Hom.: 366

Bravo AF: 0.0626

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.79
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: rs12721649; hg19: chr19-41515837;