rs1538372

Positions:

• chr1-203185404-A-G
• chr1-203185404-A-T

Variant summary

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

The NM_001276.4(CHI3L1):​c.56-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 1,612,088 control chromosomes in the GnomAD database, including 350,973 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 0.67 (34340 hom., cov: 31)
  • Exomes 𝑓: 0.66 (316633 hom.)
• Consequence: CHI3L1 NM_001276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617

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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L1	NM_001276.4	c.56-19T>C		intron_variant		ENST00000255409.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L1	ENST00000255409.8	c.56-19T>C		intron_variant		1	NM_001276.4	P1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101996 AN: 151906 Hom.: 34309 Cov.: 31

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.649

GnomAD3 exomes AF: 0.651 AC: 163038 AN: 250254 Hom.: 53254 AF XY: 0.649 AC XY: 87892 AN XY: 135336

Gnomad AFR exome AF: 0.715

Gnomad AMR exome AF: 0.629

Gnomad ASJ exome AF: 0.641

Gnomad EAS exome AF: 0.644

Gnomad SAS exome AF: 0.624

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.665

Gnomad OTH exome AF: 0.631

GnomAD4 exome AF: 0.658 AC: 960649 AN: 1460062 Hom.: 316633 Cov.: 35 AF XY: 0.656 AC XY: 476718 AN XY: 726374

Gnomad4 AFR exome AF: 0.706

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.644

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.623

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.663

Gnomad4 OTH exome AF: 0.652

GnomAD4 genome AF: 0.671 AC: 102068 AN: 152026 Hom.: 34340 Cov.: 31 AF XY: 0.670 AC XY: 49778 AN XY: 74312

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.645

Alfa AF: 0.666 Hom.: 32865

Bravo AF: 0.674

Asia WGS AF: 0.627 AC: 2182 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	7.9
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1538372; hg19: chr1-203154532;