1-203186754-G-C

Position:

• chr1-203186754-G-C

Variant summary

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

The 1-203186754-G-C 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 ENST00000255409.8 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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CHI3L1	NM_001276.4			upstream_gene_variant		ENST00000255409.8	NP_001267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8			upstream_gene_variant		1	NM_001276.4	ENSP00000255409	P1

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

Gnomad4 AMR exome AF: 0.863

Gnomad4 ASJ exome AF: 0.877

Gnomad4 EAS exome AF: 0.851

Gnomad4 SAS exome AF: 0.808

Gnomad4 FIN exome AF: 0.733

Gnomad4 NFE exome AF: 0.791

Gnomad4 OTH exome AF: 0.791

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

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.787

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

risk factor, no assertion criteria provided

literature only

OMIM

Apr 17, 2008

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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;