dbSNP rs2855658: CYP1B1:c.*975A>G (chr2-38069747-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000104.4(CYP1B1):c.*975A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 197,520 control chromosomes in the GnomAD database, including 31,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 22357 hom., cov: 31)

Exomes 𝑓: 0.61 ( 8965 hom. )

Consequence

CYP1B1
NM_000104.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.452

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-38069747-T-C is Benign according to our data. Variant chr2-38069747-T-C is described in ClinVar as [Benign]. Clinvar id is 335936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4 link	c.*975A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP1B1	ENST00000610745 link	c.*975A>G	3_prime_UTR_variant	Exon 3 of 3	1	NM_000104.4	ENSP00000478561.1	Q16678
CYP1B1	ENST00000490576 link	c.*975A>G	3_prime_UTR_variant	Exon 3 of 3	4		ENSP00000478839.2	A0A087WUQ7
CYP1B1	ENST00000491456.1 link	n.89-474A>G	intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77140

AN:

151864

Hom.:

22361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.889

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.642

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.566

Gnomad OTH

AF:

0.554

GnomAD4 exome

AF:

0.609

AC:

27717

AN:

45536

Hom.:

8965

Cov.:

AF XY:

0.609

AC XY:

12910

AN XY:

21214

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.685

Gnomad4 ASJ exome

AF:

0.507

Gnomad4 EAS exome

AF:

0.865

Gnomad4 SAS exome

AF:

0.815

Gnomad4 FIN exome

AF:

0.714

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.585

GnomAD4 genome

AF:

0.508

AC:

77151

AN:

151984

Hom.:

22357

Cov.:

AF XY:

0.522

AC XY:

38757

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.678

Gnomad4 ASJ

AF:

0.497

Gnomad4 EAS

AF:

0.889

Gnomad4 SAS

AF:

0.808

Gnomad4 FIN

AF:

0.642

Gnomad4 NFE

AF:

0.566

Gnomad4 OTH

AF:

0.557

Alfa

AF:

0.559

Hom.:

36771

Bravo

AF:

0.497

Asia WGS

AF:

0.797

AC:

2766

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glaucoma 3A

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Irido-corneo-trabecular dysgenesis

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.9

DANN

Benign

0.62

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