ENST00000946568.1:c.-131C>G

Variant names:

• chr1-203186754-G-C
• rs4950928
• ENST00000946568.1:c.-131C>G

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The ENST00000946568.1(CHI3L1):c.-131C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Note: ENST00000946568.1 is not a MANE Select or MANE Plus Clinical transcript for CHI3L1; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The gene CHI3L1 is a known oncogene (CancerMine: 7 oncogene, 2 driver citations). The gene CHI3L1 is a cancer driver gene (CancerMine: 7 oncogene, 2 driver citations). The variant allele was found at a cumulative frequency of 0.791 (AC=808,932) in the gnomAD database across 1,023,164 control chromosomes, including 321,325 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.856. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Uncertain Significance (no review stars).

• Frequency:
  • Genomes: 𝑓 0.77 (44807 hom., cov: 30)
  • Exomes 𝑓: 0.79 (276518 hom.)
• Consequence: CHI3L1 ENST00000946568.1 5_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.968
• Publications: 153 publications found

Genes affected

CHI3L1 (HGNC:1932): (chitinase 3 like 1) Chitinases catalyze the hydrolysis of chitin, which is an abundant glycopolymer found in insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 family of chitinases includes eight human family members. This gene encodes a glycoprotein member of the glycosyl hydrolase 18 family. The protein lacks chitinase activity and is secreted by activated macrophages, chondrocytes, neutrophils and synovial cells. The protein is thought to play a role in the process of inflammation and tissue remodeling. [provided by RefSeq, Sep 2009]

CHI3L1 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.856 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000946568.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CHI3L1 NM_001276.4	MANE Select	c.-131C>G	upstream_gene	N/A	Prot: NP_001267.2 UniProt:

CHI3L1 NM_001276.4

MANE Select

HGVSc / HGVSpc.-131C>G

Exon rankN/A

upstream_gene

Prot: NP_001267.2UniProt: P36222

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CHI3L1 ENST00000946568.1		c.-131C>G	5_prime_UTR	Exon 1 of 10	Prot: ENSP00000616627.1 UniProt:
	CHI3L1 ENST00000255409.8	TSL:1MANE Select	c.-131C>G	upstream_gene	N/A	Prot: ENSP00000255409.3 UniProt:
	CHI3L1 ENST00000874779.1		c.-131C>G	upstream_gene	N/A	Prot: ENSP00000544838.1 UniProt:

CHI3L1 ENST00000946568.1

HGVSc / HGVSpc.-131C>G

Exon rankExon 1 of 10

5_prime_UTR

Prot: ENSP00000616627.1UniProt: A0ACI8UDS9

CHI3L1 ENST00000255409.8

TSL:1MANE Select

HGVSc / HGVSpc.-131C>G

Exon rankN/A

upstream_gene

Prot: ENSP00000255409.3UniProt: P36222

CHI3L1 ENST00000874779.1

HGVSc / HGVSpc.-131C>G

Exon rankN/A

upstream_gene

Prot: ENSP00000544838.1UniProt: A0ACI8R3Y5

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 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.766	AC:116321	Hom:44781	AN:151856	Cov:30
GnomAD4 exome	AF: 0.795	AC:692534	Hom:276518	AN:871190	Cov:11
GnomAD4 genome	AF: 0.766	AC:116398	Hom:44807	AN:151974	Cov:30
TOPMed (Bravo)	AF: 0.772	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.681	AC:7804	Hom:2874	AN:11468	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.818	AC:1913	Hom:787	AN:2340	Cov:
ChinaMAP Phase 1	AF: 0.848	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.810	AC:243	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.793	AC:2759	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.850	AC:6148	Hom:	AN:7230	Cov:
Qatari Genome	AF: 0.881	AC:155	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.850	AC:104348	Hom:44393	AN:122752	Cov:
Turkish Variome	AF: 0.836	AC:1291	Hom:545	AN:1544	Cov:
UK10K	AF: 0.797	AC:6030	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.847	AC:7590	Hom:3225	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.646	49401	76424	0.655	88280	134696

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Asthma-related traits, susceptibility to, 7 (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	9.6
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.47
GPN-Star LLR	N/A	1.5
GPN-Star score	N/A	-1.4
PhyloP100	Benign	-0.97
PromoterAI	N/A	-0.056	Neutral

Showing 8 of 8 scores

Splicing Scores

No splicing scores have been computed for this variant.

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: rs4950928;

hg19: chr1-203155882;

COSMIC: COSV55137931;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar