Variant rs162549 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000104.4(CYP1B1):c.*2409A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 223,730 control chromosomes in the GnomAD database, including 4,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2706 hom., cov: 33)

Exomes 𝑓: 0.18 ( 1372 hom. )

Consequence

CYP1B1
NM_000104.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.654

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-38068313-T-A is Benign according to our data. Variant chr2-38068313-T-A is described in ClinVar as [Benign]. Clinvar id is 335910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 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.*2409A>T		3_prime_UTR_variant	3/3	ENST00000610745.5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
CYP1B1	ENST00000610745.5 linkuse as main transcript	c.*2409A>T	3_prime_UTR_variant	3/3	1	NM_000104.4	P1
CYP1B1	ENST00000490576.2 linkuse as main transcript	c.*2409A>T	3_prime_UTR_variant	3/3	4		P1
CYP1B1	ENST00000491456.1 linkuse as main transcript	n.184+865A>T	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27874

AN:

152024

Hom.:

2707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.201

GnomAD4 exome

AF:

0.182

AC:

13064

AN:

71588

Hom.:

1372

Cov.:

AF XY:

0.183

AC XY:

6065

AN XY:

33146

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.0169

Gnomad4 SAS exome

AF:

0.0980

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.183

AC:

27891

AN:

152142

Hom.:

2706

Cov.:

AF XY:

0.176

AC XY:

13115

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.0162

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.196

Hom.:

401

Bravo

AF:

0.189

Asia WGS

AF:

0.0790

AC:

277

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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. -

Glaucoma 3A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.2

DANN

Benign

0.75

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