rs10916

Positions:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000104.4(CYP1B1):c.*695G>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 0.779 in 201,790 control chromosomes in the GnomAD database, including 61,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.77 ( 45529 hom., cov: 30)

Exomes 𝑓: 0.80 ( 16049 hom. )

Consequence

CYP1B1
NM_000104.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.689

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-38070027-C-A is Benign according to our data. Variant chr2-38070027-C-A is described in ClinVar as [Benign]. Clinvar id is 335939.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.895 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.*695G>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.*695G>T	3_prime_UTR_variant	3/3	1	NM_000104.4	P1
CYP1B1	ENST00000490576.2 linkuse as main transcript	c.*695G>T	3_prime_UTR_variant	3/3	4		P1
CYP1B1	ENST00000491456.1 linkuse as main transcript	n.88+583G>T	intron_variant, non_coding_transcript_variant		3
CYP1B1	ENST00000494864.1 linkuse as main transcript		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.771

AC:

117086

AN:

151808

Hom.:

45509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.692

Gnomad AMR

AF:

0.874

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.913

Gnomad SAS

AF:

0.918

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.776

Gnomad OTH

AF:

0.814

GnomAD4 exome

AF:

0.801

AC:

39963

AN:

49866

Hom.:

16049

Cov.:

AF XY:

0.802

AC XY:

18669

AN XY:

23284

show subpopulations

Gnomad4 AFR exome

AF:

0.684

Gnomad4 AMR exome

AF:

0.881

Gnomad4 ASJ exome

AF:

0.743

Gnomad4 EAS exome

AF:

0.885

Gnomad4 SAS exome

AF:

0.915

Gnomad4 FIN exome

AF:

0.889

Gnomad4 NFE exome

AF:

0.787

Gnomad4 OTH exome

AF:

0.808

GnomAD4 genome

AF:

0.771

AC:

117163

AN:

151924

Hom.:

45529

Cov.:

AF XY:

0.776

AC XY:

57643

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.696

Gnomad4 AMR

AF:

0.874

Gnomad4 ASJ

AF:

0.716

Gnomad4 EAS

AF:

0.913

Gnomad4 SAS

AF:

0.918

Gnomad4 FIN

AF:

0.766

Gnomad4 NFE

AF:

0.776

Gnomad4 OTH

AF:

0.816

Alfa

AF:

0.786

Hom.:

75974

Bravo

AF:

0.776

Asia WGS

AF:

0.905

AC:

3137

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.1

DANN

Benign

0.58

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