chr1-203179453-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L1	NM_001276.4	c.1144G>A	p.Ala382Thr	missense_variant	Exon 10 of 10	ENST00000255409.8	NP_001267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L1	ENST00000255409.8	c.1144G>A	p.Ala382Thr	missense_variant	Exon 10 of 10	1	NM_001276.4	ENSP00000255409.3
CHI3L1	ENST00000404436.2	c.448G>A	p.Ala150Thr	missense_variant	Exon 4 of 4	2		ENSP00000385350.2
CHI3L1	ENST00000473185.1	n.1398G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
CHI3L1	ENST00000478742.1	n.506G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

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

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: 9.32e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs145648214; hg19: chr1-203148581;