rs34223104

Variant names:

• chr19-40991224-T-C
• rs34223104
• NM_000767.5:c.-82T>C

Variant summary

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

The NM_000767.5(CYP2B6):​c.-82T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,487,700 control chromosomes in the GnomAD database, including 174 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 0.016 (44 hom., cov: 31)
  • Exomes 𝑓: 0.010 (130 hom.)
• Consequence: CYP2B6 NM_000767.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 50 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=-1.01).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0162 (2469/152140) while in subpopulation AFR AF = 0.0295 (1221/41456). AF 95% confidence interval is 0.0281. There are 44 homozygotes in GnomAd4. There are 1216 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2469 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.-82T>C		upstream_gene_variant		ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.-82T>C		upstream_gene_variant		1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000598834.2	n.-181T>C		upstream_gene_variant		5		ENSP00000496294.1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2461 AN: 152022 Hom.: 45 Cov.: 31

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.00707

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0104 AC: 13856 AN: 1335560 Hom.: 130 Cov.: 20 AF XY: 0.0107 AC XY: 7188 AN XY: 670682

African (AFR) AF: 0.0302 AC: 924 AN: 30626

American (AMR) AF: 0.00948 AC: 413 AN: 43558

Ashkenazi Jewish (ASJ) AF: 0.0212 AC: 533 AN: 25182

East Asian (EAS) AF: 0.00139 AC: 54 AN: 38760

South Asian (SAS) AF: 0.0170 AC: 1415 AN: 83146

European-Finnish (FIN) AF: 0.00755 AC: 392 AN: 51908

Middle Eastern (MID) AF: 0.0240 AC: 129 AN: 5380

European-Non Finnish (NFE) AF: 0.00928 AC: 9292 AN: 1000780

Other (OTH) AF: 0.0125 AC: 704 AN: 56220

GnomAD4 genome AF: 0.0162 AC: 2469 AN: 152140 Hom.: 44 Cov.: 31 AF XY: 0.0164 AC XY: 1216 AN XY: 74368

African (AFR) AF: 0.0295 AC: 1221 AN: 41456

American (AMR) AF: 0.0132 AC: 202 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5176

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4816

European-Finnish (FIN) AF: 0.00707 AC: 75 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 753 AN: 68002

Other (OTH) AF: 0.0171 AC: 36 AN: 2110

Alfa AF: 0.0124 Hom.: 42

Bravo AF: 0.0172

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		-0.12
PromoterAI		0.17	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34223104; hg19: chr19-41497129;