chr2-38068461-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000104.4(CYP1B1):​c.*2261A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00707 in 225,554 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 18 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 3 hom. )

Consequence

CYP1B1
NM_000104.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0420
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 2-38068461-T-G is Benign according to our data. Variant chr2-38068461-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 898036.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00925 (1409/152308) while in subpopulation AFR AF= 0.0287 (1194/41570). AF 95% confidence interval is 0.0274. There are 18 homozygotes in gnomad4. There are 702 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP1B1NM_000104.4 linkuse as main transcriptc.*2261A>C 3_prime_UTR_variant 3/3 ENST00000610745.5 NP_000095.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP1B1ENST00000610745.5 linkuse as main transcriptc.*2261A>C 3_prime_UTR_variant 3/31 NM_000104.4 ENSP00000478561 P1
CYP1B1ENST00000490576.2 linkuse as main transcriptc.*2261A>C 3_prime_UTR_variant 3/34 ENSP00000478839 P1
CYP1B1ENST00000491456.1 linkuse as main transcriptn.184+717A>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00924
AC:
1406
AN:
152190
Hom.:
18
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0287
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0115
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.00669
GnomAD4 exome
AF:
0.00254
AC:
186
AN:
73246
Hom.:
3
Cov.:
0
AF XY:
0.00233
AC XY:
79
AN XY:
33874
show subpopulations
Gnomad4 AFR exome
AF:
0.0323
Gnomad4 AMR exome
AF:
0.00692
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000423
Gnomad4 OTH exome
AF:
0.00702
GnomAD4 genome
AF:
0.00925
AC:
1409
AN:
152308
Hom.:
18
Cov.:
33
AF XY:
0.00943
AC XY:
702
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0287
Gnomad4 AMR
AF:
0.0114
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00154
Hom.:
3
Bravo
AF:
0.0114
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Glaucoma 3A Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Irido-corneo-trabecular dysgenesis Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
7.9
DANN
Benign
0.80

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: rs77534033; hg19: chr2-38295604; API