1-203185404-A-G

Variant names:

• chr1-203185404-A-G
• rs1538372
• NM_001276.4:c.56-19T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 35 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 = 0.701 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L1	NM_001276.4	MANE Select	c.56-19T>C		intron	N/A	NP_001267.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L1	ENST00000255409.8	TSL:1 MANE Select	c.56-19T>C		intron	N/A	ENSP00000255409.3

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

GnomAD2 exomes AF: 0.651 AC: 163038 AN: 250254 AF XY: 0.649

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 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

African (AFR) AF: 0.706 AC: 23594 AN: 33436

American (AMR) AF: 0.634 AC: 28331 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 16813 AN: 26124

East Asian (EAS) AF: 0.654 AC: 25968 AN: 39678

South Asian (SAS) AF: 0.623 AC: 53657 AN: 86192

European-Finnish (FIN) AF: 0.626 AC: 33424 AN: 53378

Middle Eastern (MID) AF: 0.612 AC: 3165 AN: 5174

European-Non Finnish (NFE) AF: 0.663 AC: 736375 AN: 1111118

Other (OTH) AF: 0.652 AC: 39322 AN: 60274

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

African (AFR) AF: 0.708 AC: 29338 AN: 41456

American (AMR) AF: 0.667 AC: 10186 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2201 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3256 AN: 5136

South Asian (SAS) AF: 0.636 AC: 3067 AN: 4826

European-Finnish (FIN) AF: 0.632 AC: 6680 AN: 10566

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45085 AN: 67976

Other (OTH) AF: 0.645 AC: 1362 AN: 2110

Alfa AF: 0.666 Hom.: 42390

Bravo AF: 0.674

Asia WGS AF: 0.627 AC: 2182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.9
DANN	Benign	0.57
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1538372; hg19: chr1-203154532; COSMIC: COSV107302420; COSMIC: COSV107302420;