rs12141494

Variant names:

• chr1-203182297-G-A
• rs12141494
• NM_001276.4:c.587+434C>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.587+434C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,934 control chromosomes in the GnomAD database, including 14,441 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 0.41 (14441 hom., cov: 31)
• Consequence: CHI3L1 NM_001276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 13 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 (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L1	NM_001276.4	c.587+434C>T		intron_variant	Intron 6 of 9	ENST00000255409.8	NP_001267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8	c.587+434C>T		intron_variant	Intron 6 of 9	1	NM_001276.4	ENSP00000255409.3
CHI3L1	ENST00000404436.2	c.74+434C>T		intron_variant	Intron 1 of 3	2		ENSP00000385350.2
CHI3L1	ENST00000472064.1	n.111+434C>T		intron_variant	Intron 1 of 2	2
CHI3L1	ENST00000473185.1	n.-163C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62902 AN: 151816 Hom.: 14440 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.420

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.414 AC: 62928 AN: 151934 Hom.: 14441 Cov.: 31 AF XY: 0.415 AC XY: 30805 AN XY: 74246

African (AFR) AF: 0.220 AC: 9110 AN: 41452

American (AMR) AF: 0.344 AC: 5265 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1465 AN: 3468

East Asian (EAS) AF: 0.329 AC: 1696 AN: 5156

South Asian (SAS) AF: 0.474 AC: 2273 AN: 4798

European-Finnish (FIN) AF: 0.552 AC: 5818 AN: 10548

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35733 AN: 67918

Other (OTH) AF: 0.420 AC: 882 AN: 2102

Alfa AF: 0.461 Hom.: 2140

Bravo AF: 0.386

Asia WGS AF: 0.380 AC: 1324 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	6.2
DANN	Benign	0.66
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12141494; hg19: chr1-203151425;