2-38071060-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_000104.4(CYP1B1):c.1294C>G(p.Leu432Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,613,386 control chromosomes in the GnomAD database, including 156,236 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 21268 hom., cov: 32)

Exomes 𝑓: 0.42 ( 134968 hom. )

Consequence

CYP1B1
NM_000104.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.334

Publications

546 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 -19 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 35 curated pathogenic missense variants (we use a threshold of 10). The gene has 9 curated benign missense variants. Trascript score misZ: -2.0997 (below the threshold of 3.09). GenCC associations: The gene is linked to Peters anomaly, anterior segment dysgenesis 6, glaucoma 3A, CYP1B1-related glaucoma with or without anterior segment dysgenesis, congenital glaucoma.

BP4

Computational evidence support a benign effect (MetaRNN=0.005228162).

BP6

Variant 2-38071060-G-C is Benign according to our data. Variant chr2-38071060-G-C is described in ClinVar as Benign. ClinVar VariationId is 456637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4 link	c.1294C>G	p.Leu432Val	missense_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.1294C>G	p.Leu432Val	missense_variant	Exon 3 of 3	1	NM_000104.4	ENSP00000478561.1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74816

AN:

151976

Hom.:

21223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.446

GnomAD4 exome

AF:

0.418

AC:

610248

AN:

1461292

Hom.:

134968

Cov.:

AF XY:

0.411

AC XY:

298608

AN XY:

726824

show subpopulations

African (AFR)

AF:

0.782

AC:

26157

AN:

33464

American (AMR)

AF:

0.230

AC:

10265

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

12888

AN:

26132

East Asian (EAS)

AF:

0.125

AC:

4973

AN:

39698

South Asian (SAS)

AF:

0.220

AC:

18994

AN:

86248

European-Finnish (FIN)

AF:

0.367

AC:

19579

AN:

53410

Middle Eastern (MID)

AF:

0.344

AC:

1987

AN:

5768

European-Non Finnish (NFE)

AF:

0.441

AC:

490604

AN:

1111504

Other (OTH)

AF:

0.411

AC:

24801

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

23424

46848

70272

93696

117120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14740

29480

44220

58960

73700

<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:

0.493

AC:

74925

AN:

152094

Hom.:

21268

Cov.:

AF XY:

0.479

AC XY:

35574

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.774

AC:

32106

AN:

41478

American (AMR)

AF:

0.317

AC:

4852

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1789

AN:

3468

East Asian (EAS)

AF:

0.113

AC:

585

AN:

5184

South Asian (SAS)

AF:

0.200

AC:

966

AN:

4820

European-Finnish (FIN)

AF:

0.360

AC:

3801

AN:

10562

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.433

AC:

29445

AN:

67982

Other (OTH)

AF:

0.443

AC:

936

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1705

3411

5116

6822

8527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.421

Hom.:

10147

Bravo

AF:

0.503

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 04, 2022

Mendelics

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

AlphaMissense

Benign

0.059

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.9

(source)

DEOGEN2

Benign

0.077

T;T;T

LIST_S2

Benign

0.0

.;T;T

MetaRNN

Benign

0.0052

T;T;T

MutationAssessor

Benign

0.0

.;.;.

PhyloP100

0.33

PROVEAN

Benign

0.0

.;.;.

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;.;.

Sift4G

Benign

0.29

T;T;T

Vest4

0.053

gMVP

0.69

Splicing

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