1-203186870-G-A

Variant names:

• chr1-203186870-G-A
• rs10399805
• NM_001276.4:c.-247C>T

Variant summary

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

The NM_001276.4(CHI3L1):​c.-247C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 574,560 control chromosomes in the GnomAD database, including 11,758 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 0.22 (4964 hom., cov: 32)
  • Exomes 𝑓: 0.16 (6794 hom.)
• Consequence: CHI3L1 NM_001276.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• Publications: 48 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 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.-247C>T		upstream_gene	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.-247C>T		upstream_gene	N/A	ENSP00000255409.3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33798 AN: 151928 Hom.: 4944 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.159 AC: 67083 AN: 422512 Hom.: 6794 AF XY: 0.157 AC XY: 34740 AN XY: 221602

African (AFR) AF: 0.397 AC: 4745 AN: 11960

American (AMR) AF: 0.328 AC: 5885 AN: 17922

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 2401 AN: 13004

East Asian (EAS) AF: 0.314 AC: 9374 AN: 29900

South Asian (SAS) AF: 0.144 AC: 5988 AN: 41616

European-Finnish (FIN) AF: 0.0723 AC: 2036 AN: 28176

Middle Eastern (MID) AF: 0.194 AC: 356 AN: 1838

European-Non Finnish (NFE) AF: 0.126 AC: 31999 AN: 253572

Other (OTH) AF: 0.175 AC: 4299 AN: 24524

GnomAD4 genome AF: 0.222 AC: 33830 AN: 152048 Hom.: 4964 Cov.: 32 AF XY: 0.222 AC XY: 16490 AN XY: 74328

African (AFR) AF: 0.389 AC: 16131 AN: 41430

American (AMR) AF: 0.318 AC: 4865 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 661 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1438 AN: 5162

South Asian (SAS) AF: 0.145 AC: 700 AN: 4820

European-Finnish (FIN) AF: 0.0689 AC: 730 AN: 10588

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8632 AN: 67986

Other (OTH) AF: 0.220 AC: 462 AN: 2102

Alfa AF: 0.158 Hom.: 6964

Bravo AF: 0.253

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.64
PhyloP100		-0.53
PromoterAI		-0.063	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10399805; hg19: chr1-203155998;