1-203180945-C-T

Variant names:

• chr1-203180945-C-T
• rs2275351
• NM_001276.4:c.711+217G>A

Variant summary

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

The NM_001276.4(CHI3L1):​c.711+217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,162 control chromosomes in the GnomAD database, including 8,154 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 0.28 (8154 hom., cov: 33)
• Consequence: CHI3L1 NM_001276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L1	NM_001276.4	c.711+217G>A		intron_variant	Intron 7 of 9	ENST00000255409.8	NP_001267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8	c.711+217G>A		intron_variant	Intron 7 of 9	1	NM_001276.4	ENSP00000255409.3
CHI3L1	ENST00000404436.2	c.198+217G>A		intron_variant	Intron 2 of 3	2		ENSP00000385350.2
CHI3L1	ENST00000472064.1	n.235+217G>A		intron_variant	Intron 2 of 2	2
CHI3L1	ENST00000473185.1	n.973+217G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42923 AN: 152044 Hom.: 8134 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.282 AC: 42973 AN: 152162 Hom.: 8154 Cov.: 33 AF XY: 0.282 AC XY: 20988 AN XY: 74398

African (AFR) AF: 0.520 AC: 21562 AN: 41500

American (AMR) AF: 0.359 AC: 5498 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1954 AN: 5168

South Asian (SAS) AF: 0.221 AC: 1069 AN: 4828

European-Finnish (FIN) AF: 0.0948 AC: 1006 AN: 10614

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10308 AN: 67968

Other (OTH) AF: 0.260 AC: 548 AN: 2108

Alfa AF: 0.221 Hom.: 1881

Bravo AF: 0.316

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.68
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2275351; hg19: chr1-203150073;