chr19-40994308-T-C

Position:

• chr19-40994308-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):​c.171+2832T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,906 control chromosomes in the GnomAD database, including 7,445 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 0.30 (7445 hom., cov: 31)
• Consequence: CYP2B6 NM_000767.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.966

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.171+2832T>C		intron_variant		ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.171+2832T>C		intron_variant		1	NM_000767.5	ENSP00000324648	P1
CYP2B6	ENST00000598834.2	c.73+2832T>C		intron_variant, NMD_transcript_variant		5		ENSP00000496294

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45134 AN: 151788 Hom.: 7444 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45158 AN: 151906 Hom.: 7445 Cov.: 31 AF XY: 0.302 AC XY: 22447 AN XY: 74228

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.300

Alfa AF: 0.330 Hom.: 17208

Bravo AF: 0.291

Asia WGS AF: 0.359 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.4
DANN	Benign	0.25

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: rs8100458; hg19: chr19-41500213;