chr1-203186754-G-C

Variant names:

• chr1-203186754-G-C
• rs4950928
• NM_001276.4:c.-131C>G

Variant summary

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

The NM_001276.4(CHI3L1):​c.-131C>G variant causes a upstream gene 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 NM_001276.4 upstream_gene
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.968

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L1	NM_001276.4	c.-131C>G		upstream_gene_variant		ENST00000255409.8	NP_001267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8	c.-131C>G		upstream_gene_variant		1	NM_001276.4	ENSP00000255409.3

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

Gnomad4 AFR exome AF: 0.675 AC: 14824 AN: 21964

Gnomad4 AMR exome AF: 0.863 AC: 34559 AN: 40028

Gnomad4 ASJ exome AF: 0.877 AC: 18660 AN: 21288

Gnomad4 EAS exome AF: 0.851 AC: 31132 AN: 36594

Gnomad4 SAS exome AF: 0.808 AC: 58679 AN: 72634

Gnomad4 FIN exome AF: 0.733 AC: 30562 AN: 41706

Gnomad4 NFE exome AF: 0.791 AC: 467887 AN: 591488

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.679 AC: 0.67916 AN: 0.67916

Gnomad4 AMR AF: 0.835 AC: 0.835055 AN: 0.835055

Gnomad4 ASJ AF: 0.866 AC: 0.866282 AN: 0.866282

Gnomad4 EAS AF: 0.845 AC: 0.845483 AN: 0.845483

Gnomad4 SAS AF: 0.805 AC: 0.8047 AN: 0.8047

Gnomad4 FIN AF: 0.740 AC: 0.740383 AN: 0.740383

Gnomad4 NFE AF: 0.790 AC: 0.790051 AN: 0.790051

Gnomad4 OTH AF: 0.787 AC: 0.787405 AN: 0.787405

Alfa AF: 0.673 Hom.: 1948

Bravo AF: 0.772

Asia WGS AF: 0.793 AC: 2759 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Asthma-related traits, susceptibility to, 7 Other:1

Apr 17, 2008

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

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