1-203186575-A-T

Variant names:

• chr1-203186575-A-T
• rs7515776
• NM_001276.4:c.25+24T>A

Variant summary

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

The NM_001276.4(CHI3L1):​c.25+24T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,613,380 control chromosomes in the GnomAD database, including 26,296 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 0.23 (5649 hom., cov: 29)
  • Exomes 𝑓: 0.15 (20647 hom.)
• Consequence: CHI3L1 NM_001276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 23 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L1	NM_001276.4	c.25+24T>A		intron_variant	Intron 1 of 9	ENST00000255409.8	NP_001267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8	c.25+24T>A		intron_variant	Intron 1 of 9	1	NM_001276.4	ENSP00000255409.3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35581 AN: 151772 Hom.: 5623 Cov.: 29

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.194 AC: 48704 AN: 251056 AF XY: 0.180

Gnomad AFR exome AF: 0.446

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.292

Gnomad FIN exome AF: 0.0717

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.152 AC: 221631 AN: 1461490 Hom.: 20647 Cov.: 34 AF XY: 0.150 AC XY: 108820 AN XY: 727072

African (AFR) AF: 0.449 AC: 15038 AN: 33474

American (AMR) AF: 0.348 AC: 15542 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4723 AN: 26136

East Asian (EAS) AF: 0.305 AC: 12093 AN: 39696

South Asian (SAS) AF: 0.152 AC: 13147 AN: 86240

European-Finnish (FIN) AF: 0.0733 AC: 3913 AN: 53404

Middle Eastern (MID) AF: 0.192 AC: 1104 AN: 5764

European-Non Finnish (NFE) AF: 0.131 AC: 145612 AN: 1111676

Other (OTH) AF: 0.173 AC: 10459 AN: 60380

GnomAD4 genome AF: 0.235 AC: 35627 AN: 151890 Hom.: 5649 Cov.: 29 AF XY: 0.233 AC XY: 17329 AN XY: 74248

African (AFR) AF: 0.431 AC: 17814 AN: 41376

American (AMR) AF: 0.316 AC: 4809 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1416 AN: 5150

South Asian (SAS) AF: 0.152 AC: 733 AN: 4810

European-Finnish (FIN) AF: 0.0692 AC: 732 AN: 10584

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8796 AN: 67948

Other (OTH) AF: 0.225 AC: 475 AN: 2112

Alfa AF: 0.0975 Hom.: 185

Bravo AF: 0.265

Asia WGS AF: 0.222 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.48
PhyloP100		0.0
PromoterAI		0.027	Neutral
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: rs7515776; hg19: chr1-203155703;