2-38070372-G-T

Variant names:

• chr2-38070372-G-T
• rs162562
• NM_000104.4:c.*350C>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.*350C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 317,726 control chromosomes in the GnomAD database, including 89,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (38398 hom., cov: 33)
  • Exomes 𝑓: 0.78 (51502 hom.)
• Consequence: CYP1B1 NM_000104.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.288

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-38070372-G-T is Benign according to our data. Variant chr2-38070372-G-T is described in ClinVar as [Benign]. Clinvar id is 335944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4	c.*350C>A		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	c.*350C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_000104.4	ENSP00000478561.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104427 AN: 151962 Hom.: 38405 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.781 AC: 129450 AN: 165646 Hom.: 51502 Cov.: 0 AF XY: 0.789 AC XY: 64658 AN XY: 81986

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.862

Gnomad4 ASJ exome AF: 0.746

Gnomad4 EAS exome AF: 0.888

Gnomad4 SAS exome AF: 0.903

Gnomad4 FIN exome AF: 0.761

Gnomad4 NFE exome AF: 0.776

Gnomad4 OTH exome AF: 0.775

GnomAD4 genome AF: 0.687 AC: 104459 AN: 152080 Hom.: 38398 Cov.: 33 AF XY: 0.694 AC XY: 51636 AN XY: 74372

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.756

Alfa AF: 0.773 Hom.: 85682

Bravo AF: 0.681

Asia WGS AF: 0.868 AC: 3020 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

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. -

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	-0.90
CADD	Benign	1.3
DANN	Benign	0.51

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: rs162562; hg19: chr2-38297515;