19-41018104-A-T

Variant names:

• chr19-41018104-A-T
• rs1038376
• NM_000767.5:c.*1277A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000767.5(CYP2B6):​c.*1277A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,018 control chromosomes in the GnomAD database, including 7,634 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 0.31 (7633 hom., cov: 31)
  • Exomes 𝑓: 0.23 (1 hom.)
• Consequence: CYP2B6 NM_000767.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 18 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).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5	c.*1277A>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10	c.*1277A>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000767.5	ENSP00000324648.2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47051 AN: 151878 Hom.: 7634 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.227 AC: 5 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 5 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.125 AC: 1 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.400 AC: 4 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.310 AC: 47071 AN: 151996 Hom.: 7633 Cov.: 31 AF XY: 0.309 AC XY: 22927 AN XY: 74276

African (AFR) AF: 0.340 AC: 14063 AN: 41420

American (AMR) AF: 0.422 AC: 6450 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1385 AN: 3470

East Asian (EAS) AF: 0.158 AC: 818 AN: 5162

South Asian (SAS) AF: 0.379 AC: 1820 AN: 4804

European-Finnish (FIN) AF: 0.218 AC: 2311 AN: 10578

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19215 AN: 67974

Other (OTH) AF: 0.343 AC: 722 AN: 2108

Alfa AF: 0.290 Hom.: 881

Bravo AF: 0.324

Asia WGS AF: 0.303 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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: rs1038376; hg19: chr19-41524009;