chr1-203186754-G-C

Variant names:

• chr1-203186754-G-C
• rs4950928
• ENST00000946568.1:c.-131C>G

Variant summary

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

The ENST00000946568.1(CHI3L1):​c.-131C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 1,023,164 control chromosomes in the GnomAD database, including 321,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.77 (44807 hom., cov: 30)
  • Exomes 𝑓: 0.79 (276518 hom.)
• Consequence: CHI3L1 ENST00000946568.1 5_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.968
• Publications: 147 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000946568.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L1	NM_001276.4	MANE Select	c.-131C>G		upstream_gene	N/A	NP_001267.2	P36222

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L1	ENST00000946568.1		c.-131C>G		5_prime_UTR	Exon 1 of 10	ENSP00000616627.1
	CHI3L1	ENST00000255409.8	TSL:1 MANE Select	c.-131C>G		upstream_gene	N/A	ENSP00000255409.3	P36222
	CHI3L1	ENST00000874779.1		c.-131C>G		upstream_gene	N/A	ENSP00000544838.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116321 AN: 151856 Hom.: 44781 Cov.: 30

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 0.795 AC: 692534 AN: 871190 Hom.: 276518 Cov.: 11 AF XY: 0.796 AC XY: 360982 AN XY: 453690

African (AFR) AF: 0.675 AC: 14824 AN: 21964

American (AMR) AF: 0.863 AC: 34559 AN: 40028

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 18660 AN: 21288

East Asian (EAS) AF: 0.851 AC: 31132 AN: 36594

South Asian (SAS) AF: 0.808 AC: 58679 AN: 72634

European-Finnish (FIN) AF: 0.733 AC: 30562 AN: 41706

Middle Eastern (MID) AF: 0.847 AC: 3833 AN: 4524

European-Non Finnish (NFE) AF: 0.791 AC: 467887 AN: 591488

Other (OTH) AF: 0.791 AC: 32398 AN: 40964

GnomAD4 genome AF: 0.766 AC: 116398 AN: 151974 Hom.: 44807 Cov.: 30 AF XY: 0.768 AC XY: 57022 AN XY: 74280

African (AFR) AF: 0.679 AC: 28105 AN: 41382

American (AMR) AF: 0.835 AC: 12773 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 3006 AN: 3470

East Asian (EAS) AF: 0.845 AC: 4361 AN: 5158

South Asian (SAS) AF: 0.805 AC: 3869 AN: 4808

European-Finnish (FIN) AF: 0.740 AC: 7814 AN: 10554

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53714 AN: 67988

Other (OTH) AF: 0.787 AC: 1663 AN: 2112

Alfa AF: 0.673 Hom.: 1948

Bravo AF: 0.772

Asia WGS AF: 0.793 AC: 2759 AN: 3478

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Asthma-related traits, susceptibility to, 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.47
PhyloP100		-0.97
PromoterAI		-0.056	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4950928; hg19: chr1-203155882; COSMIC: COSV55137931;