2-38092621-C-G

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000494864.1(CYP1B1):c.-71+17048G>C 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 allele was found at a cumulative frequency of 0.63 (AC=95,840) in the gnomAD database across 152,046 control chromosomes, including 33,271 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.878. 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: 𝑓 0.63 (33271 hom., 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: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	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).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.8783 — exceeds 5%% threshold (BA1 applied)

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>C	intron	Intron 1 of 1	Prot: ENSP00000479876.1 UniProt:
	CYP1B1-AS1 ENST00000589303.6	TSL:5	n.310+16061C>G	intron	Intron 1 of 3	Prot:
	CYP1B1-AS1 ENST00000620177.4	TSL:4	n.421+16553C>G	intron	Intron 1 of 2	Prot:

CYP1B1 ENST00000494864.1

TSL:5

HGVSc / HGVSpc.-71+17048G>C

Exon rankIntron 1 of 1

intron

Prot: ENSP00000479876.1UniProt: A0A087WW26

CYP1B1-AS1 ENST00000589303.6

TSL:5

HGVSc / HGVSpn.310+16061C>G

Exon rankIntron 1 of 3

intron

Prot:

CYP1B1-AS1 ENST00000620177.4

TSL:4

HGVSc / HGVSpn.421+16553C>G

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: 0.631	AC:95817	Hom:33268	AN:151928	Cov:32
GnomAD4 genome	AF: 0.630	AC:95840	Hom:33271	AN:152046	Cov:32
TOPMed (Bravo)	AF: 0.623	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.506	AC:6165	Hom:2048	AN:12176	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.693	AC:1623	Hom:572	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.908	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.687	AC:206	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.853	AC:2967	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.895	AC:6471	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.682	AC:120	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.857	AC:105220	Hom:45091	AN:122816	Cov:
Turkish Variome	AF: 0.838	AC:1294	Hom:550	AN:1544	Cov:
UK10K	AF: 0.724	AC:5472	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.908	AC:8138	Hom:3698	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	8.8
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.36
GPN-Star LLR	N/A	-1.8
GPN-Star score	N/A	1.8
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