chr2-38092621-C-A

Variant names:

• chr2-38092621-C-A
• rs162550
• ENST00000494864.1:c.-71+17048G>T

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The ENST00000494864.1(CYP1B1):c.-71+17048G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000494864.1 is not a MANE Select or MANE Plus Clinical transcript for CYP1B1; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• Publications: 4 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: G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• congenital glaucoma

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CYP1B1-AS1 (HGNC:28543): (CYP1B1 antisense RNA 1) Predicted to enable U4 snRNA binding activity. Predicted to be involved in formation of quadruple SL/U4/U5/U6 snRNP and spliceosomal tri-snRNP complex assembly. Predicted to be part of U4/U6 x U5 tri-snRNP complex and U6 snRNP. [provided by Alliance of Genome Resources, Jul 2025]

Classification according to ACMG Germline Pathogenicity v2019

Specifications for CYP1B1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (base 0.0001, raised to 0.000401 by highest known P/LP ClinVar AF 0.000401) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000494864.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CYP1B1 ENST00000494864.1	TSL:5	c.-71+17048G>T	intron	Intron 1 of 1	Prot: ENSP00000479876.1 UniProt:
	CYP1B1-AS1 ENST00000589303.6	TSL:5	n.310+16061C>A	intron	Intron 1 of 3	Prot:
	CYP1B1-AS1 ENST00000620177.4	TSL:4	n.421+16553C>A	intron	Intron 1 of 2	Prot:

CYP1B1 ENST00000494864.1

TSL:5

HGVSc / HGVSpc.-71+17048G>T

Exon rankIntron 1 of 1

intron

Prot: ENSP00000479876.1UniProt: A0A087WW26

CYP1B1-AS1 ENST00000589303.6

TSL:5

HGVSc / HGVSpn.310+16061C>A

Exon rankIntron 1 of 3

intron

Prot:

CYP1B1-AS1 ENST00000620177.4

TSL:4

HGVSc / HGVSpn.421+16553C>A

Exon rankIntron 1 of 2

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32
TOPMed (Bravo) Warning	AF: 0.00000756	AC:2	Hom:1	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:2048	AN:12176	Cov:

Showing 4 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	15
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.51
GPN-Star LLR	N/A	-1.9
GPN-Star score	N/A	1.9
PhyloP100	Benign	0.60

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs162550;

hg19: chr2-38319763;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar