rs9341266

Positions:

• chr2-38068851-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000104.4(CYP1B1):​c.*1871C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 227,194 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (176 hom., cov: 33)
  • Exomes 𝑓: 0.046 (93 hom.)
• Consequence: CYP1B1 NM_000104.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.60

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 2-38068851-G-A is Benign according to our data. Variant chr2-38068851-G-A is described in ClinVar as [Benign]. Clinvar id is 335920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1B1	NM_000104.4	c.*1871C>T		3_prime_UTR_variant	3/3	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745	c.*1871C>T		3_prime_UTR_variant	3/3	1	NM_000104.4	ENSP00000478561.1
CYP1B1	ENST00000490576	c.*1871C>T		3_prime_UTR_variant	3/3	4		ENSP00000478839.2
CYP1B1	ENST00000491456.1	n.184+327C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5978 AN: 152046 Hom.: 176 Cov.: 33

Gnomad AFR AF: 0.00886

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.0698

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0431

GnomAD4 exome AF: 0.0458 AC: 3437 AN: 75030 Hom.: 93 Cov.: 0 AF XY: 0.0450 AC XY: 1562 AN XY: 34728

Gnomad4 AFR exome AF: 0.00855

Gnomad4 AMR exome AF: 0.0273

Gnomad4 ASJ exome AF: 0.0709

Gnomad4 EAS exome AF: 0.0404

Gnomad4 SAS exome AF: 0.0997

Gnomad4 FIN exome AF: 0.0814

Gnomad4 NFE exome AF: 0.0474

Gnomad4 OTH exome AF: 0.0462

GnomAD4 genome AF: 0.0392 AC: 5972 AN: 152164 Hom.: 176 Cov.: 33 AF XY: 0.0420 AC XY: 3127 AN XY: 74368

Gnomad4 AFR AF: 0.00884

Gnomad4 AMR AF: 0.0399

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.0701

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.0747

Gnomad4 NFE AF: 0.0443

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0453 Hom.: 267

Bravo AF: 0.0345

Asia WGS AF: 0.0690 AC: 239 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Irido-corneo-trabecular dysgenesis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

Glaucoma 3A Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.4
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs9341266; hg19: chr2-38295994;