rs2617266

Positions:

chr2-38075401-G-A

Variant summary

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

The NM_000104.4(CYP1B1):c.-1-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,609,792 control chromosomes in the GnomAD database, including 66,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6311 hom., cov: 33)

Exomes 𝑓: 0.28 ( 59724 hom. )

Consequence

CYP1B1
NM_000104.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001679

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0280

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 (BayesDel_noAF=-0.76).

BP6

Variant 2-38075401-G-A is Benign according to our data. Variant chr2-38075401-G-A is described in ClinVar as [Benign]. Clinvar id is 166974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-38075401-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 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.-1-12C>T		splice_polypyrimidine_tract_variant, intron_variant		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.-1-12C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000104.4	ENSP00000478561	P1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42994

AN:

152072

Hom.:

6305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.506

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.265

GnomAD3 exomes

AF:

0.293

AC:

70960

AN:

242504

Hom.:

10583

AF XY:

0.297

AC XY:

39066

AN XY:

131754

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.283

AC:

412441

AN:

1457602

Hom.:

59724

Cov.:

AF XY:

0.286

AC XY:

207294

AN XY:

724966

show subpopulations

Gnomad4 AFR exome

AF:

0.262

Gnomad4 AMR exome

AF:

0.294

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.148

Gnomad4 SAS exome

AF:

0.368

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.279

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.283

AC:

43021

AN:

152190

Hom.:

6311

Cov.:

AF XY:

0.288

AC XY:

21429

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.284

Hom.:

1257

Bravo

AF:

0.271

Asia WGS

AF:

0.296

AC:

1028

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	Jan 12, 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	- -

not provided

Benign:2

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

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 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.040

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