1-203186754-G-A

Variant names:

• chr1-203186754-G-A
• rs4950928
• ENST00000946568.1:c.-131C>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 ENST00000946568.1(CHI3L1):c.-131C>T 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 variant allele was found at a cumulative frequency of 0.0000132 (AC=2) in the gnomAD database across 152,042 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.00000488. 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 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHI3L1 ENST00000946568.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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 ACMG Germline Pathogenicity v2019

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		Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.00000488 — very rare for unknown gene (threshold 0.001) — 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: 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>T	upstream_gene	N/A	Prot: NP_001267.2 UniProt:

CHI3L1 NM_001276.4

MANE Select

HGVSc / HGVSpc.-131C>T

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>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	Prot: ENSP00000616627.1 UniProt:
	CHI3L1 ENST00000946568.1		c.-131C>T	5_prime_UTR	Exon 1 of 10	Prot: ENSP00000616627.1 UniProt:
	CHI3L1 ENST00000255409.8	TSL:1MANE Select	c.-131C>T	upstream_gene	N/A	Prot: ENSP00000255409.3 UniProt:

CHI3L1 ENST00000946568.1

HGVSc / HGVSpc.-131C>T

Exon rankExon 1 of 10

5_prime_UTR_premature_start_codon_gain

Prot: ENSP00000616627.1UniProt: A0ACI8UDS9

CHI3L1 ENST00000946568.1

HGVSc / HGVSpc.-131C>T

Exon rankExon 1 of 10

5_prime_UTR

Prot: ENSP00000616627.1UniProt: A0ACI8UDS9

CHI3L1 ENST00000255409.8

TSL:1MANE Select

HGVSc / HGVSpc.-131C>T

Exon rankN/A

upstream_gene

Prot: ENSP00000255409.3UniProt: P36222

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: 0.0000132	AC:2	Hom:0	AN:151924	Cov:30
GnomAD4 exome Warning	AF: 0.0000195	AC:17	Hom:0	AN:872254	Cov:11
GnomAD4 genome	AF: 0.0000132	AC:2	Hom:0	AN:152042	Cov:30
TOPMed (Bravo) Warning	AF: 0.000476	AC:126	Hom:2	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:2874	AN:11468	Cov:
Local & regional cohorts 1 source Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.00	AC:0	Hom:0	AN:88	Cov:

Showing 6 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	6.8
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.92
GPN-Star LLR	N/A	-0.98
GPN-Star score	N/A	0.98
PhyloP100	Benign	-0.97
PromoterAI	N/A	-0.18	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;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar