chr1-203182048-G-A

Variant names:

• chr1-203182048-G-A
• rs7542294
• NM_001276.4:c.587+683C>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+683C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,322 control chromosomes in the GnomAD database, including 7,833 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 (7832 hom., cov: 32)
  • Exomes 𝑓: 0.099 (1 hom.)
• Consequence: CHI3L1 NM_001276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• 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 (AFR) allele frequency at 95% confidence interval = 0.495 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.587+683C>T		intron	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.587+683C>T		intron	N/A	ENSP00000255409.3
	CHI3L1	ENST00000473185.1	TSL:2	n.87C>T		non_coding_transcript_exon	Exon 1 of 2
	CHI3L1	ENST00000404436.2	TSL:2	c.74+683C>T		intron	N/A	ENSP00000385350.2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42328 AN: 151974 Hom.: 7813 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.0991 AC: 23 AN: 232 Hom.: 1 Cov.: 0 AF XY: 0.107 AC XY: 13 AN XY: 122

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.100 AC: 1 AN: 10

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.333 AC: 2 AN: 6

European-Finnish (FIN) AF: 0.143 AC: 2 AN: 14

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0957 AC: 18 AN: 188

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.279 AC: 42377 AN: 152090 Hom.: 7832 Cov.: 32 AF XY: 0.279 AC XY: 20715 AN XY: 74362

African (AFR) AF: 0.500 AC: 20740 AN: 41458

American (AMR) AF: 0.359 AC: 5479 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2188 AN: 5170

South Asian (SAS) AF: 0.224 AC: 1077 AN: 4818

European-Finnish (FIN) AF: 0.0948 AC: 1003 AN: 10584

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

European-Non Finnish (NFE) AF: 0.152 AC: 10315 AN: 67992

Other (OTH) AF: 0.258 AC: 546 AN: 2114

Alfa AF: 0.199 Hom.: 12452

Bravo AF: 0.312

Asia WGS AF: 0.337 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.62
PhyloP100		-0.047
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: rs7542294; hg19: chr1-203151176;