2-38074660-C-G

Position:

chr2-38074660-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000104.4(CYP1B1):c.729G>C(p.Val243=) 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

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 made for transcript

Verdict is Benign. Variant got -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 id is 166972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-38074660-C-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
CYP1B1	NM_000104.4 linkuse as main transcript	c.729G>C	p.Val243=	synonymous_variant	2/3	ENST00000610745.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP1B1	ENST00000610745.5 linkuse as main transcript	c.729G>C	p.Val243=	synonymous_variant	2/3	1	NM_000104.4	P1

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

GnomAD3 exomes

AF:

0.0179

AC:

4425

AN:

247312

Hom.:

381

AF XY:

0.0131

AC XY:

1762

AN XY:

134388

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 SAS exome

AF:

0.00141

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

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.0137

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.00882

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.000456

Gnomad4 NFE exome

AF:

0.000860

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0640

AC:

9746

AN:

152328

Hom.:

1009

Cov.:

AF XY:

0.0614

AC XY:

4576

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0217

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00946

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.0459

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 24, 2014

- -

Glaucoma 3A

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. -

Irido-corneo-trabecular dysgenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Congenital glaucoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.3

DANN

Benign

0.86

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