rs2617266

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000104.4(CYP1B1):c.-1-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,609,792 control chromosomes in the GnomAD database, including 66,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6311 hom., cov: 33)

Exomes 𝑓: 0.28 ( 59724 hom. )

Consequence

CYP1B1
NM_000104.4 intron

Scores

Splicing: ADA: 0.00001679

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0280

Publications

34 publications found

Variant links:

Genes affected

CYP1B1 (HGNC:2597): (cytochrome P450 family 1 subfamily B member 1) This gene 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. The enzyme encoded by this gene localizes to the endoplasmic reticulum and metabolizes procarcinogens such as polycyclic aromatic hydrocarbons and 17beta-estradiol. Mutations in this gene have been associated with primary congenital glaucoma; therefore it is thought that the enzyme also metabolizes a signaling molecule involved in eye development, possibly a steroid. [provided by RefSeq, Jul 2008]

CYP1B1 links:

CYP1B1-AS1 (HGNC:28543): (CYP1B1 antisense RNA 1)

CYP1B1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 2-38075401-G-A is Benign according to our data. Variant chr2-38075401-G-A is described in ClinVar as Benign. ClinVar VariationId is 166974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4 link	c.-1-12C>T		intron_variant	Intron 1 of 2	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5 link	c.-1-12C>T		intron_variant	Intron 1 of 2	1	NM_000104.4	ENSP00000478561.1		Q16678

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42994

AN:

152072

Hom.:

6305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.506

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.265

GnomAD2 exomes

AF:

0.293

AC:

70960

AN:

242504

AF XY:

0.297

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.283

AC:

412441

AN:

1457602

Hom.:

59724

Cov.:

AF XY:

0.286

AC XY:

207294

AN XY:

724966

show subpopulations

African (AFR)

AF:

0.262

AC:

8749

AN:

33412

American (AMR)

AF:

0.294

AC:

13070

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

5839

AN:

26078

East Asian (EAS)

AF:

0.148

AC:

5872

AN:

39648

South Asian (SAS)

AF:

0.368

AC:

31571

AN:

85848

European-Finnish (FIN)

AF:

0.358

AC:

18550

AN:

51804

Middle Eastern (MID)

AF:

0.307

AC:

1442

AN:

4690

European-Non Finnish (NFE)

AF:

0.279

AC:

310442

AN:

1111448

Other (OTH)

AF:

0.281

AC:

16906

AN:

60174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

17861

35723

53584

71446

89307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10326

20652

30978

41304

51630

<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:

0.283

AC:

43021

AN:

152190

Hom.:

6311

Cov.:

AF XY:

0.288

AC XY:

21429

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.258

AC:

10726

AN:

41528

American (AMR)

AF:

0.292

AC:

4475

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

724

AN:

3470

East Asian (EAS)

AF:

0.180

AC:

930

AN:

5156

South Asian (SAS)

AF:

0.379

AC:

1830

AN:

4826

European-Finnish (FIN)

AF:

0.366

AC:

3877

AN:

10590

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.285

AC:

19347

AN:

67998

Other (OTH)

AF:

0.272

AC:

575

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1583

3166

4748

6331

7914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.284

Hom.:

1257

Bravo

AF:

0.271

Asia WGS

AF:

0.296

AC:

1028

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 14, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glaucoma 3A

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Anterior segment dysgenesis 6

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Irido-corneo-trabecular dysgenesis

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.028

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over