Genetic Variant CHI3L2:p.Ile73Val (chr1-111230888-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004000.3(CHI3L2):c.217A>G(p.Ile73Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,884 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. I73F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CHI3L2
NM_004000.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Publications

0 publications found

Variant links:

Genes affected

CHI3L2 (HGNC:1933): (chitinase 3 like 2) The protein encoded by this gene is similar to bacterial chitinases but lacks chitinase activity. The encoded protein is secreted and is involved in cartilage biogenesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CHI3L2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.067099124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3 link	c.217A>G	p.Ile73Val	missense_variant	Exon 3 of 11	ENST00000369748.9	NP_003991.2	Q15782-4
CHI3L2	NM_001025197.1 link	c.187A>G	p.Ile63Val	missense_variant	Exon 2 of 10		NP_001020368.1	Q15782-6
CHI3L2	NM_001025199.2 link	c.-21A>G		5_prime_UTR_variant	Exon 2 of 10		NP_001020370.1	Q15782-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9 link	c.217A>G	p.Ile73Val	missense_variant	Exon 3 of 11	1	NM_004000.3	ENSP00000358763.4		Q15782-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0035

T;.;T;.;T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.57

.;T;T;T;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.067

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.86

L;.;.;.;L;.

PhyloP100

1.2

PrimateAI

Benign

0.32

PROVEAN

Benign

0.65

N;N;N;N;N;N

REVEL

Benign

0.057

Sift

Benign

0.037

D;T;T;T;D;D

Sift4G

Benign

0.24

T;T;T;T;T;T

Polyphen

0.53

P;.;.;.;P;.

Vest4

0.059

MutPred

0.44

Gain of methylation at K74 (P = 0.0629);Gain of methylation at K74 (P = 0.0629);Gain of methylation at K74 (P = 0.0629);.;Gain of methylation at K74 (P = 0.0629);Gain of methylation at K74 (P = 0.0629);

MVP

0.17

MPC

0.017

ClinPred

0.096

GERP RS

0.015

PromoterAI

0.037

Neutral

(source)

Varity_R

0.34

gMVP

0.38

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr1-111230888-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over