Genetic Variant CYP2B6:c.1153-6C>T (chr19-41012668-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000767.5(CYP2B6):c.1153-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,613,298 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 43 hom. )

Consequence

CYP2B6
NM_000767.5 splice_region, intron

Scores

Splicing: ADA: 0.0004234

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.558

Publications

0 publications found

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]

CYP2B6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-41012668-C-T is Benign according to our data. Variant chr19-41012668-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3024890.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 778 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5 link	c.1153-6C>T		splice_region_variant, intron_variant	Intron 7 of 8	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CYP2B6	ENST00000324071.10 link	c.1153-6C>T	splice_region_variant, intron_variant	Intron 7 of 8	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000597612.1 link	n.647+183C>T	intron_variant	Intron 2 of 2	1
CYP2B6	ENST00000593831.1 link	c.445-6C>T	splice_region_variant, intron_variant	Intron 3 of 4	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2 link	n.*593+183C>T	intron_variant	Intron 8 of 9	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

779

AN:

151832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00315

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0176

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00639

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00535

AC:

1344

AN:

251230

AF XY:

0.00554

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0180

Gnomad NFE exome

AF:

0.00670

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00513

AC:

7493

AN:

1461350

Hom.:

Cov.:

AF XY:

0.00508

AC XY:

3696

AN XY:

726976

show subpopulations

African (AFR)

AF:

0.000929

AC:

AN:

33358

American (AMR)

AF:

0.00219

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00429

AC:

112

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00121

AC:

104

AN:

86246

European-Finnish (FIN)

AF:

0.0169

AC:

902

AN:

53304

Middle Eastern (MID)

AF:

0.00246

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00540

AC:

6001

AN:

1111898

Other (OTH)

AF:

0.00381

AC:

230

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

429

857

1286

1714

2143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00512

AC:

778

AN:

151948

Hom.:

Cov.:

AF XY:

0.00534

AC XY:

397

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.00218

AC:

AN:

41274

American (AMR)

AF:

0.00314

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0176

AC:

186

AN:

10594

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00640

AC:

435

AN:

68018

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00654

Hom.:

EpiCase

AF:

0.00747

EpiControl

AF:

0.00539

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CYP2B6: BP4, BS2

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.4

(source)

DANN

Benign

0.47

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00042

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over