chr1-203180582-A-C

Variant names:

• chr1-203180582-A-C
• NM_001276.4:c.782T>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001276.4(CHI3L1):​c.782T>G​(p.Phe261Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F261S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHI3L1 NM_001276.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L1	NM_001276.4	c.782T>G	p.Phe261Cys	missense_variant	Exon 8 of 10	ENST00000255409.8	NP_001267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8	c.782T>G	p.Phe261Cys	missense_variant	Exon 8 of 10	1	NM_001276.4	ENSP00000255409.3
CHI3L1	ENST00000404436.2	c.198+580T>G		intron_variant	Intron 2 of 3	2		ENSP00000385350.2
CHI3L1	ENST00000472064.1	n.306T>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
CHI3L1	ENST00000473185.1	n.973+580T>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460268 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726432

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.93		Loss of stability (P = 0.1132);
MVP		0.74
MPC		0.49
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.90
gMVP		0.68

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-203149710;