chr19-41016164-G-C

Position:

• chr19-41016164-G-C

Variant summary

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

The ENST00000324071.10(CYP2B6):​c.1295-482G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,910 control chromosomes in the GnomAD database, including 6,088 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 0.26 (6088 hom., cov: 30)
• Consequence: CYP2B6 ENST00000324071.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.688

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.1295-482G>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.1295-482G>C		intron_variant		1	NM_000767.5	ENSP00000324648	P1
CYP2B6	ENST00000597612.1	n.648-482G>C		intron_variant, non_coding_transcript_variant		1
CYP2B6	ENST00000593831.1	c.587-482G>C		intron_variant		2		ENSP00000470582
CYP2B6	ENST00000598834.2	c.*652-482G>C		intron_variant, NMD_transcript_variant		5		ENSP00000496294

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39269 AN: 151790 Hom.: 6087 Cov.: 30

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.365

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.259 AC: 39277 AN: 151910 Hom.: 6088 Cov.: 30 AF XY: 0.265 AC XY: 19668 AN XY: 74220

Gnomad4 AFR AF: 0.0870

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.275

Alfa AF: 0.170 Hom.: 389

Bravo AF: 0.254

Asia WGS AF: 0.341 AC: 1187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.64

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: rs8109848; hg19: chr19-41522069;