rs145648214

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-203179453-C-A
• chr1-203179453-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001276.4(CHI3L1):​c.1144G>T​(p.Ala382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,536,866 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: CHI3L1 NM_001276.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031738997).

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>T	p.Ala382Ser	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>T	p.Ala382Ser	missense	Exon 10 of 10	ENSP00000255409.3	P36222
	CHI3L1	ENST00000874779.1		c.1354G>T	p.Ala452Ser	missense	Exon 12 of 12	ENSP00000544838.1
	CHI3L1	ENST00000874774.1		c.1162G>T	p.Ala388Ser	missense	Exon 10 of 10	ENSP00000544833.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000412 AC: 8 AN: 194018 AF XY: 0.0000195

Gnomad AFR exome AF: 0.000449

Gnomad AMR exome AF: 0.0000395

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: 0.0000130 AC: 18 AN: 1384598 Hom.: 0 Cov.: 29 AF XY: 0.00000736 AC XY: 5 AN XY: 679790

African (AFR) AF: 0.000386 AC: 12 AN: 31096

American (AMR) AF: 0.0000880 AC: 3 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: 0.00 AC: 0 AN: 1073152

Other (OTH) AF: 0.0000528 AC: 3 AN: 56844

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74446

African (AFR) AF: 0.000674 AC: 28 AN: 41548

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000230 Hom.: 0

Bravo AF: 0.000261

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000414 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.8
DANN	Benign	0.69
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.18	N
PhyloP100		0.94
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.080
Sift	Benign	0.87	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.082
MVP		0.24
MPC		0.064
ClinPred		0.0060	T
GERP RS		3.5
Varity_R		0.060
gMVP		0.11
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;