rs8192718

Variant names:

• chr19-41009909-G-A
• rs8192718
• ENST00000597612.1:n.233G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41009909-G-A
• chr19-41009909-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000597612.1(CYP2B6):​n.233G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,570,734 control chromosomes in the GnomAD database, including 222 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 0.012 (22 hom., cov: 31)
  • Exomes 𝑓: 0.013 (200 hom.)
• Consequence: CYP2B6 ENST00000597612.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 5 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).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0115 (1756/152272) while in subpopulation EAS AF = 0.0481 (249/5180). AF 95% confidence interval is 0.0432. There are 22 homozygotes in GnomAd4. There are 874 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1756 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000597612.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	NM_000767.5	MANE Select	c.823-85G>A		intron	N/A	NP_000758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2B6	ENST00000597612.1	TSL:1	n.233G>A		non_coding_transcript_exon	Exon 1 of 3
	CYP2B6	ENST00000324071.10	TSL:1 MANE Select	c.823-85G>A		intron	N/A	ENSP00000324648.2
	CYP2B6	ENST00000593831.1	TSL:2	c.257-2389G>A		intron	N/A	ENSP00000470582.1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1754 AN: 152154 Hom.: 22 Cov.: 31

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.0128 AC: 18213 AN: 1418462 Hom.: 200 Cov.: 25 AF XY: 0.0134 AC XY: 9493 AN XY: 707634

African (AFR) AF: 0.00156 AC: 51 AN: 32692

American (AMR) AF: 0.00779 AC: 343 AN: 44056

Ashkenazi Jewish (ASJ) AF: 0.00509 AC: 131 AN: 25734

East Asian (EAS) AF: 0.0327 AC: 1288 AN: 39408

South Asian (SAS) AF: 0.0259 AC: 2185 AN: 84450

European-Finnish (FIN) AF: 0.0107 AC: 524 AN: 49084

Middle Eastern (MID) AF: 0.0239 AC: 136 AN: 5692

European-Non Finnish (NFE) AF: 0.0117 AC: 12623 AN: 1078254

Other (OTH) AF: 0.0158 AC: 932 AN: 59092

GnomAD4 genome AF: 0.0115 AC: 1756 AN: 152272 Hom.: 22 Cov.: 31 AF XY: 0.0117 AC XY: 874 AN XY: 74466

African (AFR) AF: 0.00226 AC: 94 AN: 41558

American (AMR) AF: 0.0112 AC: 171 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.0481 AC: 249 AN: 5180

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4828

European-Finnish (FIN) AF: 0.0108 AC: 115 AN: 10610

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 918 AN: 68012

Other (OTH) AF: 0.0147 AC: 31 AN: 2106

Alfa AF: 0.0125 Hom.: 34

Bravo AF: 0.0108

Asia WGS AF: 0.0320 AC: 112 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.52
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism

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: rs8192718; hg19: chr19-41515814;