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rs9341249

chr2-38074660-C-Gchr2-38074660-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000104.4(CYP1B1):c.729G>C(p.Val243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,613,280 control chromosomes in the GnomAD database, including 1,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 1009 hom., cov: 33)
Exomes 𝑓: 0.0073 ( 861 hom. )

Consequence

CYP1B1
NM_000104.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.501
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 -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-38074660-C-G is Benign according to our data. Variant chr2-38074660-C-G is described in ClinVar as [Benign]. Clinvar id is 166972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-38074660-C-G is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.501 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP1B1NM_000104.4 linkuse as main transcriptc.729G>C p.Val243= synonymous_variant 2/3 ENST00000610745.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP1B1ENST00000610745.5 linkuse as main transcriptc.729G>C p.Val243= synonymous_variant 2/31 NM_000104.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0638
AC:
9716
AN:
152210
Hom.:
1003
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.219
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0218
Gnomad ASJ
AF:
0.00461
Gnomad EAS
AF:
0.00943
Gnomad SAS
AF:
0.00310
Gnomad FIN
AF:
0.000753
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00151
Gnomad OTH
AF:
0.0464
GnomAD3 exomes
AF:
0.0179
AC:
4425
AN:
247312
Hom.:
381
AF XY:
0.0131
AC XY:
1762
AN XY:
134388
show subpopulations
Gnomad AFR exome
AF:
0.221
Gnomad AMR exome
AF:
0.0128
Gnomad ASJ exome
AF:
0.00502
Gnomad EAS exome
AF:
0.00983
Gnomad SAS exome
AF:
0.00141
Gnomad FIN exome
AF:
0.000512
Gnomad NFE exome
AF:
0.00139
Gnomad OTH exome
AF:
0.00891
GnomAD4 exome
AF:
0.00728
AC:
10635
AN:
1460952
Hom.:
861
Cov.:
31
AF XY:
0.00644
AC XY:
4682
AN XY:
726766
show subpopulations
Gnomad4 AFR exome
AF:
0.221
Gnomad4 AMR exome
AF:
0.0137
Gnomad4 ASJ exome
AF:
0.00379
Gnomad4 EAS exome
AF:
0.00882
Gnomad4 SAS exome
AF:
0.00139
Gnomad4 FIN exome
AF:
0.000456
Gnomad4 NFE exome
AF:
0.000860
Gnomad4 OTH exome
AF:
0.0163
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0640
AC:
9746
AN:
152328
Hom.:
1009
Cov.:
33
AF XY:
0.0614
AC XY:
4576
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.220
Gnomad4 AMR
AF:
0.0217
Gnomad4 ASJ
AF:
0.00461
Gnomad4 EAS
AF:
0.00946
Gnomad4 SAS
AF:
0.00290
Gnomad4 FIN
AF:
0.000753
Gnomad4 NFE
AF:
0.00151
Gnomad4 OTH
AF:
0.0459
Alfa
AF:
0.0183
Hom.:
73
Bravo
AF:
0.0722
Asia WGS
AF:
0.0220
AC:
76
AN:
3478
EpiCase
AF:
0.00125
EpiControl
AF:
0.00219

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Apr 24, 2014- -
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. -
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. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Congenital glaucoma Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
9.3
Dann
Benign
0.86

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: rs9341249; hg19: chr2-38301803; API