rs1056837

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000104.4(CYP1B1):c.1347T>C(p.Asp449Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,613,842 control chromosomes in the GnomAD database, including 278,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 22657 hom., cov: 32)

Exomes 𝑓: 0.58 ( 256281 hom. )

Consequence

CYP1B1
NM_000104.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.811

Publications

106 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 Gene-Disease associations (from GenCC):

CYP1B1-related glaucoma with or without anterior segment dysgenesis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
glaucoma 3A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
anterior segment dysgenesis 6
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
congenital glaucoma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Peters anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CYP1B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-38071007-A-G is Benign according to our data. Variant chr2-38071007-A-G is described in ClinVar as Benign. ClinVar VariationId is 166970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.811 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4 link	c.1347T>C	p.Asp449Asp	synonymous_variant	Exon 3 of 3	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5 link	c.1347T>C	p.Asp449Asp	synonymous_variant	Exon 3 of 3	1	NM_000104.4	ENSP00000478561.1		Q16678

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78162

AN:

151956

Hom.:

22655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.686

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.889

Gnomad SAS

AF:

0.800

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.561

GnomAD2 exomes

AF:

0.634

AC:

159422

AN:

251432

AF XY:

0.643

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.785

Gnomad ASJ exome

AF:

0.508

Gnomad EAS exome

AF:

0.901

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.634

GnomAD4 exome

AF:

0.584

AC:

853195

AN:

1461768

Hom.:

256281

Cov.:

AF XY:

0.590

AC XY:

429343

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.243

AC:

8136

AN:

33478

American (AMR)

AF:

0.772

AC:

34517

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

13296

AN:

26132

East Asian (EAS)

AF:

0.875

AC:

34741

AN:

39700

South Asian (SAS)

AF:

0.780

AC:

67318

AN:

86254

European-Finnish (FIN)

AF:

0.633

AC:

33839

AN:

53418

Middle Eastern (MID)

AF:

0.661

AC:

3811

AN:

5768

European-Non Finnish (NFE)

AF:

0.559

AC:

621828

AN:

1111900

Other (OTH)

AF:

0.591

AC:

35709

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

21559

43118

64678

86237

107796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17414

34828

52242

69656

87070

<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:

0.514

AC:

78186

AN:

152074

Hom.:

22657

Cov.:

AF XY:

0.528

AC XY:

39236

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.248

AC:

10287

AN:

41484

American (AMR)

AF:

0.686

AC:

10485

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1692

AN:

3466

East Asian (EAS)

AF:

0.889

AC:

4602

AN:

5178

South Asian (SAS)

AF:

0.801

AC:

3846

AN:

4804

European-Finnish (FIN)

AF:

0.640

AC:

6762

AN:

10564

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.567

AC:

38554

AN:

67972

Other (OTH)

AF:

0.564

AC:

1191

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1715

3431

5146

6862

8577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.557

Hom.:

80293

Bravo

AF:

0.504

Asia WGS

AF:

0.793

AC:

2756

AN:

3478

EpiCase

AF:

0.575

EpiControl

AF:

0.579

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 05, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glaucoma 3A

Benign:2

Jan 13, 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 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital glaucoma

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.92

CADD

Benign

0.66

(source)

DANN

Benign

0.34

PhyloP100

-0.81

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over