19-41010277-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000767.5(CYP2B6):​c.964+142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 967,550 control chromosomes in the GnomAD database, including 35,555 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 ( 7279 hom., cov: 31)
Exomes 𝑓: 0.26 ( 28276 hom. )

Consequence

CYP2B6
NM_000767.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.194
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP2B6NM_000767.5 linkuse as main transcriptc.964+142C>T intron_variant ENST00000324071.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP2B6ENST00000324071.10 linkuse as main transcriptc.964+142C>T intron_variant 1 NM_000767.5 P1P20813-1
CYP2B6ENST00000597612.1 linkuse as main transcriptn.459+142C>T intron_variant, non_coding_transcript_variant 1
CYP2B6ENST00000593831.1 linkuse as main transcriptc.257-2021C>T intron_variant 2
CYP2B6ENST00000598834.2 linkuse as main transcriptc.*405+142C>T intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.297
AC:
45114
AN:
151908
Hom.:
7279
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.407
Gnomad AMI
AF:
0.107
Gnomad AMR
AF:
0.344
Gnomad ASJ
AF:
0.263
Gnomad EAS
AF:
0.208
Gnomad SAS
AF:
0.379
Gnomad FIN
AF:
0.191
Gnomad MID
AF:
0.297
Gnomad NFE
AF:
0.241
Gnomad OTH
AF:
0.303
GnomAD4 exome
AF:
0.255
AC:
208244
AN:
815524
Hom.:
28276
AF XY:
0.260
AC XY:
108653
AN XY:
417512
show subpopulations
Gnomad4 AFR exome
AF:
0.413
Gnomad4 AMR exome
AF:
0.316
Gnomad4 ASJ exome
AF:
0.264
Gnomad4 EAS exome
AF:
0.188
Gnomad4 SAS exome
AF:
0.385
Gnomad4 FIN exome
AF:
0.194
Gnomad4 NFE exome
AF:
0.240
Gnomad4 OTH exome
AF:
0.263
GnomAD4 genome
AF:
0.297
AC:
45131
AN:
152026
Hom.:
7279
Cov.:
31
AF XY:
0.297
AC XY:
22036
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.406
Gnomad4 AMR
AF:
0.344
Gnomad4 ASJ
AF:
0.263
Gnomad4 EAS
AF:
0.207
Gnomad4 SAS
AF:
0.377
Gnomad4 FIN
AF:
0.191
Gnomad4 NFE
AF:
0.241
Gnomad4 OTH
AF:
0.306
Alfa
AF:
0.141
Hom.:
243
Bravo
AF:
0.309
Asia WGS
AF:
0.319
AC:
1105
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
4.7
DANN
Benign
0.33

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2306606; hg19: chr19-41516182; COSMIC: COSV57845978; COSMIC: COSV57845978; API