dbSNP rs2551188: CYP1B1:c.-2+129G>A (chr2-38075651-C-T) – 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.-2+129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 573,238 control chromosomes in the GnomAD database, including 28,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9695 hom., cov: 34)

Exomes 𝑓: 0.29 ( 19192 hom. )

Consequence

CYP1B1
NM_000104.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.170

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 2-38075651-C-T is Benign according to our data. Variant chr2-38075651-C-T is described in ClinVar as [Benign]. Clinvar id is 1248456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4 link	c.-2+129G>A		intron_variant	Intron 1 of 2	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5 link	c.-2+129G>A		intron_variant	Intron 1 of 2	1	NM_000104.4	ENSP00000478561.1		Q16678

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52459

AN:

152066

Hom.:

9675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.312

GnomAD4 exome

AF:

0.294

AC:

123761

AN:

421056

Hom.:

19192

Cov.:

AF XY:

0.297

AC XY:

65660

AN XY:

221092

show subpopulations

Gnomad4 AFR exome

AF:

0.480

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.229

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.365

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.285

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.345

AC:

52525

AN:

152182

Hom.:

9695

Cov.:

AF XY:

0.349

AC XY:

25975

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.367

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.301

Hom.:

7383

Bravo

AF:

0.342

Asia WGS

AF:

0.312

AC:

1083

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.6

DANN

Benign

0.82

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