1-203186952-T-C

Variant names:

• chr1-203186952-T-C
• rs10399931
• NM_001276.4:c.-329A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001276.4(CHI3L1):​c.-329A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,044 control chromosomes in the GnomAD database, including 41,087 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (41087 hom., cov: 31)
• Consequence: CHI3L1 NM_001276.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 78 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

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.-329A>G		upstream_gene	N/A	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.-329A>G		upstream_gene	N/A	ENSP00000255409.3	P36222
	CHI3L1	ENST00000874779.1		c.-329A>G		upstream_gene	N/A	ENSP00000544838.1
	CHI3L1	ENST00000874774.1		c.-329A>G		upstream_gene	N/A	ENSP00000544833.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111553 AN: 151926 Hom.: 41064 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.739

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.734 AC: 111618 AN: 152044 Hom.: 41087 Cov.: 31 AF XY: 0.733 AC XY: 54479 AN XY: 74324

African (AFR) AF: 0.708 AC: 29310 AN: 41422

American (AMR) AF: 0.740 AC: 11317 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2820 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3369 AN: 5174

South Asian (SAS) AF: 0.731 AC: 3525 AN: 4824

European-Finnish (FIN) AF: 0.721 AC: 7606 AN: 10554

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51104 AN: 67994

Other (OTH) AF: 0.733 AC: 1550 AN: 2114

Alfa AF: 0.741 Hom.: 80341

Bravo AF: 0.733

Asia WGS AF: 0.673 AC: 2339 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.39
PromoterAI		0.16	Neutral

Splicing

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

Other links and lift over

dbSNP: rs10399931; hg19: chr1-203156080;