rs880633

Variant names:

• chr1-203183673-T-C
• rs880633
• NM_001276.4:c.433A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001276.4(CHI3L1):​c.433A>G​(p.Arg145Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,613,670 control chromosomes in the GnomAD database, including 199,632 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.41 (14516 hom., cov: 32)
  • Exomes 𝑓: 0.50 (185116 hom.)
• Consequence: CHI3L1 NM_001276.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004434228).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L1	NM_001276.4	c.433A>G	p.Arg145Gly	missense_variant	Exon 5 of 10	ENST00000255409.8	NP_001267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8	c.433A>G	p.Arg145Gly	missense_variant	Exon 5 of 10	1	NM_001276.4	ENSP00000255409.3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63070 AN: 151910 Hom.: 14515 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.419

GnomAD3 exomes AF: 0.450 AC: 113050 AN: 251364 Hom.: 27267 AF XY: 0.463 AC XY: 62963 AN XY: 135856

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.434

Gnomad EAS exome AF: 0.375

Gnomad SAS exome AF: 0.467

Gnomad FIN exome AF: 0.545

Gnomad NFE exome AF: 0.531

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.498 AC: 727640 AN: 1461642 Hom.: 185116 Cov.: 48 AF XY: 0.499 AC XY: 362705 AN XY: 727134

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.469

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.415 AC: 63088 AN: 152028 Hom.: 14516 Cov.: 32 AF XY: 0.416 AC XY: 30914 AN XY: 74306

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.419

Alfa AF: 0.500 Hom.: 49846

Bravo AF: 0.386

TwinsUK AF: 0.524 AC: 1943

ALSPAC AF: 0.519 AC: 2000

ESP6500AA AF: 0.220 AC: 968

ESP6500EA AF: 0.514 AC: 4422

ExAC AF: 0.455 AC: 55239

Asia WGS AF: 0.396 AC: 1381 AN: 3478

EpiCase AF: 0.519

EpiControl AF: 0.526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.098
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.85	P
Vest4		0.085
MPC		0.23
ClinPred		0.020	T
GERP RS		5.7
Varity_R		0.60
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs880633; hg19: chr1-203152801; COSMIC: COSV55139863; COSMIC: COSV55139863;