rs1056837

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000104.4(CYP1B1):c.1347T>C(p.Asp449=) 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:10

Conservation

PhyloP100: -0.811

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 166970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-38071007-A-G is described in Lovd as [Benign]. Variant chr2-38071007-A-G is described in Lovd as [Likely_benign].

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/exons	MANE	UniProt
CYP1B1	NM_000104.4 linkuse as main transcript	c.1347T>C	p.Asp449=	synonymous_variant	3/3	ENST00000610745.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP1B1	ENST00000610745.5 linkuse as main transcript	c.1347T>C	p.Asp449=	synonymous_variant	3/3	1	NM_000104.4	P1

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

GnomAD3 exomes

AF:

0.634

AC:

159422

AN:

251432

Hom.:

53689

AF XY:

0.643

AC XY:

87363

AN XY:

135890

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 SAS exome

AF:

0.787

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

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.772

Gnomad4 ASJ exome

AF:

0.509

Gnomad4 EAS exome

AF:

0.875

Gnomad4 SAS exome

AF:

0.780

Gnomad4 FIN exome

AF:

0.633

Gnomad4 NFE exome

AF:

0.559

Gnomad4 OTH exome

AF:

0.591

GnomAD4 genome

AF:

0.514

AC:

78186

AN:

152074

Hom.:

22657

Cov.:

AF XY:

0.528

AC XY:

39236

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.686

Gnomad4 ASJ

AF:

0.488

Gnomad4 EAS

AF:

0.889

Gnomad4 SAS

AF:

0.801

Gnomad4 FIN

AF:

0.640

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.564

Alfa

AF:

0.563

Hom.:

55479

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:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 05, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Glaucoma 3A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

Anterior segment dysgenesis 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Irido-corneo-trabecular dysgenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Congenital glaucoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

Cadd

Benign

0.66

Dann

Benign

0.34

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

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