Genetic Variant NM_000767.5:c.646-17C>T (chr19-41009202-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000767.5(CYP2B6):c.646-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00996 in 1,607,186 control chromosomes in the GnomAD database, including 1,157 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 0.051 ( 618 hom., cov: 26)

Exomes 𝑓: 0.0057 ( 539 hom. )

Consequence

CYP2B6
NM_000767.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.196

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5 link	c.646-17C>T		intron_variant	Intron 4 of 8	ENST00000324071.10	NP_000758.1	P20813-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP2B6	ENST00000324071.10 link	c.646-17C>T	intron_variant	Intron 4 of 8	1	NM_000767.5	ENSP00000324648.2	P20813-1
CYP2B6	ENST00000593831.1 link	c.257-3096C>T	intron_variant	Intron 2 of 4	2		ENSP00000470582.1	M0QZJ2
CYP2B6	ENST00000598834.2 link	n.*87-17C>T	intron_variant	Intron 5 of 9	5		ENSP00000496294.1	A0A2R8YFA4

Frequencies

GnomAD3 genomes

AF:

0.0510

AC:

7689

AN:

150648

Hom.:

614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0269

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00127

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.000884

Gnomad OTH

AF:

0.0380

GnomAD2 exomes

AF:

0.0136

AC:

3334

AN:

245904

AF XY:

0.00985

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.00453

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.00835

GnomAD4 exome

AF:

0.00569

AC:

8291

AN:

1456422

Hom.:

539

Cov.:

AF XY:

0.00497

AC XY:

3604

AN XY:

724854

show subpopulations

African (AFR)

AF:

0.174

AC:

5777

AN:

33270

American (AMR)

AF:

0.0133

AC:

594

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00525

AC:

137

AN:

26074

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39678

South Asian (SAS)

AF:

0.000360

AC:

AN:

86106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.000717

AC:

794

AN:

1107286

Other (OTH)

AF:

0.0145

AC:

876

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

353

706

1060

1413

1766

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:

0.0512

AC:

7719

AN:

150764

Hom.:

618

Cov.:

AF XY:

0.0496

AC XY:

3647

AN XY:

73562

show subpopulations

African (AFR)

AF:

0.175

AC:

7152

AN:

40754

American (AMR)

AF:

0.0268

AC:

404

AN:

15066

Ashkenazi Jewish (ASJ)

AF:

0.00404

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00127

AC:

AN:

4716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10490

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000884

AC:

AN:

67842

Other (OTH)

AF:

0.0376

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

278

556

833

1111

1389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.00873

Hom.:

Bravo

AF:

0.0597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.7

(source)

DANN

Benign

0.74

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over