rs28399502

Positions:

• chr19-41016965-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000767.5(CYP2B6):​c.*138C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 836,634 control chromosomes in the GnomAD database, including 43 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 0.010 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (17 hom.)
• Consequence: CYP2B6 NM_000767.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1597/152276) while in subpopulation AFR AF= 0.0369 (1534/41550). AF 95% confidence interval is 0.0354. There are 26 homozygotes in gnomad4. There are 775 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1597 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5	c.*138C>A		3_prime_UTR_variant	9/9	ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10	c.*138C>A		3_prime_UTR_variant	9/9	1	NM_000767.5	P1
CYP2B6	ENST00000597612.1	n.967C>A		non_coding_transcript_exon_variant	3/3	1
CYP2B6	ENST00000593831.1	c.*138C>A		3_prime_UTR_variant	5/5	2
CYP2B6	ENST00000598834.2	c.*971C>A		3_prime_UTR_variant, NMD_transcript_variant	10/10	5

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1586 AN: 152158 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.00121 AC: 825 AN: 684358 Hom.: 17 Cov.: 9 AF XY: 0.00103 AC XY: 360 AN XY: 349684

Gnomad4 AFR exome AF: 0.0363

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00125

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000361

Gnomad4 OTH exome AF: 0.00260

GnomAD4 genome AF: 0.0105 AC: 1597 AN: 152276 Hom.: 26 Cov.: 32 AF XY: 0.0104 AC XY: 775 AN XY: 74460

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00200 Hom.: 6

Bravo AF: 0.0122

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs28399502; hg19: chr19-41522870;