1-203179515-C-T

Variant names:

• chr1-203179515-C-T
• rs370960745
• NM_001276.4:c.1082G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001276.4(CHI3L1):​c.1082G>A​(p.Gly361Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000924 in 1,590,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000095 (0 hom.)
• Consequence: CHI3L1 NM_001276.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53
• Publications: 2 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.826

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.1082G>A	p.Gly361Asp	missense	Exon 10 of 10	NP_001267.2	P36222

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L1	ENST00000255409.8	TSL:1 MANE Select	c.1082G>A	p.Gly361Asp	missense	Exon 10 of 10	ENSP00000255409.3	P36222
	CHI3L1	ENST00000874779.1		c.1292G>A	p.Gly431Asp	missense	Exon 12 of 12	ENSP00000544838.1
	CHI3L1	ENST00000874774.1		c.1100G>A	p.Gly367Asp	missense	Exon 10 of 10	ENSP00000544833.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000841 AC: 20 AN: 237772 AF XY: 0.0000934

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000239

Gnomad NFE exome AF: 0.000138

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000946 AC: 136 AN: 1437958 Hom.: 0 Cov.: 34 AF XY: 0.000101 AC XY: 72 AN XY: 712338

African (AFR) AF: 0.00 AC: 0 AN: 32588

American (AMR) AF: 0.00 AC: 0 AN: 41630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24674

East Asian (EAS) AF: 0.00 AC: 0 AN: 39302

South Asian (SAS) AF: 0.0000238 AC: 2 AN: 83930

European-Finnish (FIN) AF: 0.0000757 AC: 4 AN: 52840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.000117 AC: 129 AN: 1098240

Other (OTH) AF: 0.0000169 AC: 1 AN: 59126

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000125 Hom.: 0

Bravo AF: 0.0000907

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.5
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.48
MPC		0.45
ClinPred		0.88	D
GERP RS		2.8
Varity_R		0.90
gMVP		0.49
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs370960745; hg19: chr1-203148643;