Genetic Variant CHI3L1:p.Thr293Ala (chr1-203180487-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001276.4(CHI3L1):c.877A>G(p.Thr293Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CHI3L1
NM_001276.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.647

Publications

0 publications found

Variant links:

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)

CHI3L1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21966031).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L1	NM_001276.4	MANE Select	c.877A>G	p.Thr293Ala	missense	Exon 8 of 10	NP_001267.2	P36222

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHI3L1	ENST00000255409.8	TSL:1 MANE Select	c.877A>G	p.Thr293Ala	missense	Exon 8 of 10	ENSP00000255409.3	P36222
CHI3L1	ENST00000874779.1		c.1087A>G	p.Thr363Ala	missense	Exon 10 of 12	ENSP00000544838.1
CHI3L1	ENST00000874774.1		c.895A>G	p.Thr299Ala	missense	Exon 8 of 10	ENSP00000544833.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32080

American (AMR)

AF:

0.00

AC:

AN:

40292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25352

East Asian (EAS)

AF:

0.00

AC:

AN:

37918

South Asian (SAS)

AF:

0.00

AC:

AN:

83768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105098

Other (OTH)

AF:

0.00

AC:

AN:

59486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.85

M_CAP

Benign

0.0078

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

PhyloP100

0.65

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.92

REVEL

Benign

0.080

Sift

Uncertain

0.016

Sift4G

Benign

0.062

Polyphen

0.16

Vest4

0.19

MutPred

0.54

Gain of ubiquitination at K289 (P = 0.1047)

MVP

0.43

MPC

0.091

ClinPred

0.29

GERP RS

4.4

Varity_R

0.61

gMVP

0.26

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over