2-38074825-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000104.4(CYP1B1):​c.564C>A​(p.Gly188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,567,192 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 123 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 116 hom. )

Consequence

CYP1B1
NM_000104.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.06
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-AS1 (HGNC:28543): (CYP1B1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 2-38074825-G-T is Benign according to our data. Variant chr2-38074825-G-T is described in ClinVar as [Benign]. Clinvar id is 166973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.06 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP1B1NM_000104.4 linkuse as main transcriptc.564C>A p.Gly188= synonymous_variant 2/3 ENST00000610745.5 NP_000095.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP1B1ENST00000610745.5 linkuse as main transcriptc.564C>A p.Gly188= synonymous_variant 2/31 NM_000104.4 ENSP00000478561 P1

Frequencies

GnomAD3 genomes
AF:
0.0223
AC:
3395
AN:
152206
Hom.:
124
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0779
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00746
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00321
Gnomad NFE
AF:
0.000367
Gnomad OTH
AF:
0.0129
GnomAD3 exomes
AF:
0.00489
AC:
793
AN:
162086
Hom.:
32
AF XY:
0.00364
AC XY:
324
AN XY:
89032
show subpopulations
Gnomad AFR exome
AF:
0.0811
Gnomad AMR exome
AF:
0.00367
Gnomad ASJ exome
AF:
0.000126
Gnomad EAS exome
AF:
0.0000804
Gnomad SAS exome
AF:
0.000125
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000224
Gnomad OTH exome
AF:
0.000676
GnomAD4 exome
AF:
0.00216
AC:
3062
AN:
1414868
Hom.:
116
Cov.:
31
AF XY:
0.00180
AC XY:
1259
AN XY:
699656
show subpopulations
Gnomad4 AFR exome
AF:
0.0781
Gnomad4 AMR exome
AF:
0.00416
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000742
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000873
Gnomad4 OTH exome
AF:
0.00434
GnomAD4 genome
AF:
0.0223
AC:
3397
AN:
152324
Hom.:
123
Cov.:
33
AF XY:
0.0220
AC XY:
1638
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0777
Gnomad4 AMR
AF:
0.00745
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000367
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.00148
Hom.:
5
Bravo
AF:
0.0254
Asia WGS
AF:
0.00404
AC:
14
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Apr 24, 2014- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Irido-corneo-trabecular dysgenesis Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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. -
Congenital glaucoma Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
6.7
DANN
Benign
0.84

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.

Other links and lift over

dbSNP: rs9341247; hg19: chr2-38301968; API