chr1-203179453-C-T

Variant names:

• chr1-203179453-C-T
• rs145648214
• NM_001276.4:c.1144G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001276.4(CHI3L1):​c.1144G>A​(p.Ala382Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. A382S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CHI3L1 NM_001276.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.941
• Publications: 2 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]

MYBPH (HGNC:7552): (myosin binding protein H) Predicted to be a structural constituent of muscle. Predicted to be involved in regulation of striated muscle contraction. Predicted to be located in myosin filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08522132).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L1	NM_001276.4	MANE Select	c.1144G>A	p.Ala382Thr	missense	Exon 10 of 10	NP_001267.2	P36222

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L1	ENST00000255409.8	TSL:1 MANE Select	c.1144G>A	p.Ala382Thr	missense	Exon 10 of 10	ENSP00000255409.3	P36222
	CHI3L1	ENST00000874779.1		c.1354G>A	p.Ala452Thr	missense	Exon 12 of 12	ENSP00000544838.1
	CHI3L1	ENST00000874774.1		c.1162G>A	p.Ala388Thr	missense	Exon 10 of 10	ENSP00000544833.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 194018 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384598 Hom.: 0 Cov.: 29 AF XY: 0.00000147 AC XY: 1 AN XY: 679790

African (AFR) AF: 0.00 AC: 0 AN: 31096

American (AMR) AF: 0.00 AC: 0 AN: 34100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20820

East Asian (EAS) AF: 0.00 AC: 0 AN: 38952

South Asian (SAS) AF: 0.00 AC: 0 AN: 73878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5372

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1073152

Other (OTH) AF: 0.00 AC: 0 AN: 56844

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.80
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.94
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.033
Sift	Benign	0.34	T
Sift4G	Benign	0.22	T
Polyphen		0.082	B
Vest4		0.074
MutPred		0.28		Gain of glycosylation at A382 (P = 0.0099)
MVP		0.25
MPC		0.075
ClinPred		0.18	T
GERP RS		3.5
Varity_R		0.049
gMVP		0.11
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs145648214; hg19: chr1-203148581;