chr1-203181080-G-A

Variant names:

• chr1-203181080-G-A
• rs2275353
• NM_001276.4:c.711+82C>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+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,554,482 control chromosomes in the GnomAD database, including 36,373 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 (7748 hom., cov: 32)
  • Exomes 𝑓: 0.18 (28625 hom.)
• Consequence: CHI3L1 NM_001276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L1	NM_001276.4	c.711+82C>T		intron_variant	Intron 7 of 9	ENST00000255409.8	NP_001267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8	c.711+82C>T		intron_variant	Intron 7 of 9	1	NM_001276.4	ENSP00000255409.3
CHI3L1	ENST00000404436.2	c.198+82C>T		intron_variant	Intron 2 of 3	2		ENSP00000385350.2
CHI3L1	ENST00000472064.1	n.235+82C>T		intron_variant	Intron 2 of 2	2
CHI3L1	ENST00000473185.1	n.973+82C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42097 AN: 151968 Hom.: 7729 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.181 AC: 253808 AN: 1402396 Hom.: 28625 AF XY: 0.180 AC XY: 125036 AN XY: 695448

African (AFR) AF: 0.506 AC: 16375 AN: 32336

American (AMR) AF: 0.407 AC: 17239 AN: 42318

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5308 AN: 23402

East Asian (EAS) AF: 0.432 AC: 16921 AN: 39124

South Asian (SAS) AF: 0.219 AC: 17230 AN: 78742

European-Finnish (FIN) AF: 0.0946 AC: 4846 AN: 51214

Middle Eastern (MID) AF: 0.206 AC: 1047 AN: 5088

European-Non Finnish (NFE) AF: 0.152 AC: 162476 AN: 1072078

Other (OTH) AF: 0.213 AC: 12366 AN: 58094

GnomAD4 genome AF: 0.277 AC: 42146 AN: 152086 Hom.: 7748 Cov.: 32 AF XY: 0.277 AC XY: 20596 AN XY: 74360

African (AFR) AF: 0.501 AC: 20782 AN: 41446

American (AMR) AF: 0.358 AC: 5468 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1951 AN: 5148

South Asian (SAS) AF: 0.222 AC: 1073 AN: 4830

European-Finnish (FIN) AF: 0.0945 AC: 1003 AN: 10618

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

European-Non Finnish (NFE) AF: 0.151 AC: 10298 AN: 67980

Other (OTH) AF: 0.257 AC: 543 AN: 2114

Alfa AF: 0.234 Hom.: 2234

Bravo AF: 0.310

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.48
PhyloP100		-0.12
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

Other links and lift over

dbSNP: rs2275353; hg19: chr1-203150208; COSMIC: COSV55137942; COSMIC: COSV55137942;