rs2275352

Variant names:

• chr1-203181051-G-A
• rs2275352
• NM_001276.4:c.711+111C>T

Variant summary

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

The NM_001276.4(CHI3L1):​c.711+111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,375,366 control chromosomes in the GnomAD database, including 32,528 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 0.28 (8068 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24460 hom.)
• Consequence: CHI3L1 NM_001276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.511 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.711+111C>T		intron	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.711+111C>T		intron	N/A	ENSP00000255409.3	P36222
	CHI3L1	ENST00000874779.1		c.921+111C>T		intron	N/A	ENSP00000544838.1
	CHI3L1	ENST00000874774.1		c.729+111C>T		intron	N/A	ENSP00000544833.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42735 AN: 151980 Hom.: 8049 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.180 AC: 219738 AN: 1223268 Hom.: 24460 AF XY: 0.179 AC XY: 108059 AN XY: 604144

African (AFR) AF: 0.521 AC: 14022 AN: 26926

American (AMR) AF: 0.399 AC: 11191 AN: 28052

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 4305 AN: 19072

East Asian (EAS) AF: 0.435 AC: 15649 AN: 35948

South Asian (SAS) AF: 0.217 AC: 13764 AN: 63462

European-Finnish (FIN) AF: 0.0950 AC: 4395 AN: 46262

Middle Eastern (MID) AF: 0.216 AC: 841 AN: 3902

European-Non Finnish (NFE) AF: 0.153 AC: 144651 AN: 948346

Other (OTH) AF: 0.213 AC: 10920 AN: 51298

GnomAD4 genome AF: 0.281 AC: 42786 AN: 152098 Hom.: 8068 Cov.: 32 AF XY: 0.281 AC XY: 20885 AN XY: 74374

African (AFR) AF: 0.516 AC: 21394 AN: 41432

American (AMR) AF: 0.359 AC: 5487 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1950 AN: 5150

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4828

European-Finnish (FIN) AF: 0.0947 AC: 1006 AN: 10618

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10302 AN: 67994

Other (OTH) AF: 0.259 AC: 547 AN: 2116

Alfa AF: 0.272 Hom.: 1628

Bravo AF: 0.315

Asia WGS AF: 0.321 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.27
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2275352;

hg19: chr1-203150179;

COSMIC: COSV55137032;

COSMIC: COSV55137032;