rs1056827

Positions:

chr2-38075034-C-A

Variant summary

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

The ENST00000610745.5(CYP1B1):c.355G>T(p.Ala119Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,588,118 control chromosomes in the GnomAD database, including 73,925 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 0.35 ( 9842 hom., cov: 34)

Exomes 𝑓: 0.29 ( 64083 hom. )

Consequence

CYP1B1
ENST00000610745.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.503

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=1.7783786E-5).

BP6

Variant 2-38075034-C-A is Benign according to our data. Variant chr2-38075034-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 92437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-38075034-C-A is described in Lovd as [Benign]. Variant chr2-38075034-C-A is described in Lovd as [Pathogenic].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1B1	NM_000104.4 linkuse as main transcript	c.355G>T	p.Ala119Ser	missense_variant	2/3	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5 linkuse as main transcript	c.355G>T	p.Ala119Ser	missense_variant	2/3	1	NM_000104.4	ENSP00000478561	P1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52919

AN:

152028

Hom.:

9823

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.346

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.317

GnomAD3 exomes

AF:

0.319

AC:

65208

AN:

204494

Hom.:

10661

AF XY:

0.320

AC XY:

36476

AN XY:

114044

show subpopulations

Gnomad AFR exome

AF:

0.490

Gnomad AMR exome

AF:

0.317

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.385

Gnomad FIN exome

AF:

0.366

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.294

AC:

422171

AN:

1435970

Hom.:

64083

Cov.:

AF XY:

0.296

AC XY:

211668

AN XY:

713932

show subpopulations

Gnomad4 AFR exome

AF:

0.489

Gnomad4 AMR exome

AF:

0.314

Gnomad4 ASJ exome

AF:

0.231

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.348

AC:

52986

AN:

152148

Hom.:

9842

Cov.:

AF XY:

0.352

AC XY:

26171

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.474

Gnomad4 AMR

AF:

0.320

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.385

Gnomad4 FIN

AF:

0.365

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.298

Hom.:

4539

Bravo

AF:

0.345

TwinsUK

AF:

0.259

AC:

960

ALSPAC

AF:

0.280

AC:

1080

ESP6500AA

AF:

0.452

AC:

1833

ESP6500EA

AF:

0.278

AC:

2239

ExAC

AF:

0.305

AC:

35266

Asia WGS

AF:

0.313

AC:

1089

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 14, 2013	- -

Glaucoma 3A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 26681220, 25619313, 26283052, 10739169, 18575334, 23861929, 18573508, 11854439, 22177211, 19820397, 24591815, 19383894, 15958554) -

Anterior segment dysgenesis 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Glaucoma 3, primary infantile, B;C1856439:Glaucoma 3A;C4310623:Anterior segment dysgenesis 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 28, 2022

- -

Congenital glaucoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.7

DANN

Benign

0.83

DEOGEN2

Benign

0.069

T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.34

.;T;T

MetaRNN

Benign

0.000018

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.55

N;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.28

Sift4G

Benign

0.16

T;T;.

Vest4

0.022

ClinPred

0.000019

GERP RS

-0.88

Varity_R

0.053

gMVP

0.59

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