rs9341249

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000104.4(CYP1B1):c.729G>C(p.Val243Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,613,280 control chromosomes in the GnomAD database, including 1,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 1009 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 861 hom. )

Consequence

CYP1B1
NM_000104.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.501

Publications

19 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 2-38074660-C-G is Benign according to our data. Variant chr2-38074660-C-G is described in ClinVar as Benign. ClinVar VariationId is 166972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.501 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4 link	c.729G>C	p.Val243Val	synonymous_variant	Exon 2 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.729G>C	p.Val243Val	synonymous_variant	Exon 2 of 3	1	NM_000104.4	ENSP00000478561.1		Q16678

Frequencies

GnomAD3 genomes

AF:

0.0638

AC:

9716

AN:

152210

Hom.:

1003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0218

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00943

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.0464

GnomAD2 exomes

AF:

0.0179

AC:

4425

AN:

247312

AF XY:

0.0131

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.00502

Gnomad EAS exome

AF:

0.00983

Gnomad FIN exome

AF:

0.000512

Gnomad NFE exome

AF:

0.00139

Gnomad OTH exome

AF:

0.00891

GnomAD4 exome

AF:

0.00728

AC:

10635

AN:

1460952

Hom.:

861

Cov.:

AF XY:

0.00644

AC XY:

4682

AN XY:

726766

show subpopulations

African (AFR)

AF:

0.221

AC:

7401

AN:

33476

American (AMR)

AF:

0.0137

AC:

612

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00379

AC:

AN:

26122

East Asian (EAS)

AF:

0.00882

AC:

350

AN:

39700

South Asian (SAS)

AF:

0.00139

AC:

120

AN:

86238

European-Finnish (FIN)

AF:

0.000456

AC:

AN:

52576

Middle Eastern (MID)

AF:

0.0149

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000860

AC:

956

AN:

1111982

Other (OTH)

AF:

0.0163

AC:

987

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

710

1421

2131

2842

3552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

236

472

708

944

1180

<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:

0.0640

AC:

9746

AN:

152328

Hom.:

1009

Cov.:

AF XY:

0.0614

AC XY:

4576

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.220

AC:

9123

AN:

41556

American (AMR)

AF:

0.0217

AC:

332

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.00946

AC:

AN:

5182

South Asian (SAS)

AF:

0.00290

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00151

AC:

103

AN:

68034

Other (OTH)

AF:

0.0459

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

404

808

1213

1617

2021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0183

Hom.:

Bravo

AF:

0.0722

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Apr 24, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glaucoma 3A

Benign:1

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. -

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

Jan 23, 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

-0.45

CADD

Benign

9.3

(source)

DANN

Benign

0.86

PhyloP100

-0.50

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