Variant rs35449271 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5 link	c.1153-6C>T		splice_region_variant, intron_variant		ENST00000324071.10	NP_000758.1	P20813-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CYP2B6	ENST00000324071.10 link	c.1153-6C>T	splice_region_variant, intron_variant	1	NM_000767.5	ENSP00000324648.2	P20813-1
CYP2B6	ENST00000597612.1 link	n.647+183C>T	intron_variant	1
CYP2B6	ENST00000593831.1 link	c.445-6C>T	splice_region_variant, intron_variant	2		ENSP00000470582.1	M0QZJ2
CYP2B6	ENST00000598834.2 link	n.*593+183C>T	intron_variant	5		ENSP00000496294.1	A0A2R8YFA4

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

GnomAD3 exomes

AF:

0.00535

AC:

1344

AN:

251230

Hom.:

AF XY:

0.00554

AC XY:

752

AN XY:

135792

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 SAS exome

AF:

0.00137

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

Gnomad4 AFR exome

AF:

0.000929

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.0169

Gnomad4 NFE exome

AF:

0.00540

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.00512

AC:

778

AN:

151948

Hom.:

Cov.:

AF XY:

0.00534

AC XY:

397

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00218

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0176

Gnomad4 NFE

AF:

0.00640

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00557

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

CYP2B6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.4

DANN

Benign

0.47

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over