rs10916

Variant names:

• chr2-38070027-C-A
• rs10916
• NM_000104.4:c.*695G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-38070027-C-A
• chr2-38070027-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000104.4(CYP1B1):​c.*695G>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 0.779 in 201,790 control chromosomes in the GnomAD database, including 61,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45529 hom., cov: 30)
  • Exomes 𝑓: 0.80 (16049 hom.)
• Consequence: CYP1B1 NM_000104.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.689
• Publications: 33 publications found

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 Gene-Disease associations (from GenCC):

• CYP1B1-related glaucoma with or without anterior segment dysgenesis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• glaucoma 3A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
• anterior segment dysgenesis 6

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• congenital glaucoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Peters anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-38070027-C-A is Benign according to our data. Variant chr2-38070027-C-A is described in ClinVar as Benign. ClinVar VariationId is 335939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4	c.*695G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5	c.*695G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_000104.4	ENSP00000478561.1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117086 AN: 151808 Hom.: 45509 Cov.: 30

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.814

GnomAD4 exome AF: 0.801 AC: 39963 AN: 49866 Hom.: 16049 Cov.: 0 AF XY: 0.802 AC XY: 18669 AN XY: 23284

African (AFR) AF: 0.684 AC: 1516 AN: 2216

American (AMR) AF: 0.881 AC: 1278 AN: 1450

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2396 AN: 3224

East Asian (EAS) AF: 0.885 AC: 6897 AN: 7796

South Asian (SAS) AF: 0.915 AC: 388 AN: 424

European-Finnish (FIN) AF: 0.889 AC: 32 AN: 36

Middle Eastern (MID) AF: 0.881 AC: 275 AN: 312

European-Non Finnish (NFE) AF: 0.787 AC: 23834 AN: 30266

Other (OTH) AF: 0.808 AC: 3347 AN: 4142

GnomAD4 genome AF: 0.771 AC: 117163 AN: 151924 Hom.: 45529 Cov.: 30 AF XY: 0.776 AC XY: 57643 AN XY: 74264

African (AFR) AF: 0.696 AC: 28830 AN: 41400

American (AMR) AF: 0.874 AC: 13346 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2481 AN: 3466

East Asian (EAS) AF: 0.913 AC: 4730 AN: 5182

South Asian (SAS) AF: 0.918 AC: 4424 AN: 4820

European-Finnish (FIN) AF: 0.766 AC: 8063 AN: 10532

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52686 AN: 67936

Other (OTH) AF: 0.816 AC: 1722 AN: 2110

Alfa AF: 0.781 Hom.: 180541

Bravo AF: 0.776

Asia WGS AF: 0.905 AC: 3137 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Irido-corneo-trabecular dysgenesis Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.58
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10916; hg19: chr2-38297170;