2-38075247-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000104.4(CYP1B1):c.142C>G(p.Arg48Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,593,196 control chromosomes in the GnomAD database, including 74,187 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10687 hom., cov: 34)

Exomes 𝑓: 0.29 ( 63500 hom. )

Consequence

CYP1B1
NM_000104.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.744

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.667002E-5).

BP6

Variant 2-38075247-G-C is Benign according to our data. Variant chr2-38075247-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 92436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-38075247-G-C is described in Lovd as [Benign]. Variant chr2-38075247-G-C is described in Lovd as [Pathogenic].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4 link	c.142C>G	p.Arg48Gly	missense_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.142C>G	p.Arg48Gly	missense_variant	Exon 2 of 3	1	NM_000104.4	ENSP00000478561.1		Q16678

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54437

AN:

152054

Hom.:

10663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.516

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.320

GnomAD3 exomes

AF:

0.312

AC:

67344

AN:

215506

Hom.:

10980

AF XY:

0.311

AC XY:

36611

AN XY:

117740

show subpopulations

Gnomad AFR exome

AF:

0.516

Gnomad AMR exome

AF:

0.312

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.190

Gnomad SAS exome

AF:

0.375

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.297

GnomAD4 exome

AF:

0.291

AC:

419924

AN:

1441022

Hom.:

63500

Cov.:

AF XY:

0.293

AC XY:

210007

AN XY:

715810

show subpopulations

Gnomad4 AFR exome

AF:

0.526

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.148

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.358

AC:

54510

AN:

152174

Hom.:

10687

Cov.:

AF XY:

0.362

AC XY:

26908

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.516

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.367

Gnomad4 NFE

AF:

0.287

Gnomad4 OTH

AF:

0.326

Alfa

AF:

0.242

Hom.:

869

Bravo

AF:

0.356

TwinsUK

AF:

0.258

AC:

957

ALSPAC

AF:

0.278

AC:

1071

ESP6500AA

AF:

0.506

AC:

2205

ESP6500EA

AF:

0.270

AC:

2313

ExAC

AF:

0.301

AC:

35804

Asia WGS

AF:

0.315

AC:

1094

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 14, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Glaucoma 3A

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

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: Likely 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

This variant is associated with the following publications: (PMID: 15958554, 11854439, 18573508, 10910054) -

Anterior segment dysgenesis 6

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

0.066

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.7

DANN

Benign

0.40

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.10

.;T;T

MetaRNN

Benign

0.000077

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Benign

0.46

Sift4G

Benign

0.29

T;T;.

Vest4

0.030

ClinPred

0.000019

GERP RS

-4.8

Varity_R

0.070

gMVP

0.48

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