dbSNP rs7542034: CHI3L2:p.Thr317Thr (chr1-111241359-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004000.3(CHI3L2):c.951G>A(p.Thr317Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,602,084 control chromosomes in the GnomAD database, including 1,406 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.055 ( 692 hom., cov: 32)

Exomes 𝑓: 0.0089 ( 714 hom. )

Consequence

CHI3L2
NM_004000.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.04

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-3.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CHI3L2	NM_004000.3 link	c.951G>A	p.Thr317Thr	synonymous_variant	Exon 9 of 11	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1 link	c.921G>A	p.Thr307Thr	synonymous_variant	Exon 8 of 10		NP_001020368.1
CHI3L2	NM_001025199.2 link	c.714G>A	p.Thr238Thr	synonymous_variant	Exon 8 of 10		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9 link	c.951G>A	p.Thr317Thr	synonymous_variant	Exon 9 of 11	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes

AF:

0.0547

AC:

8325

AN:

152066

Hom.:

680

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0262

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.0191

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.0459

GnomAD2 exomes

AF:

0.0196

AC:

4929

AN:

251438

AF XY:

0.0164

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.0182

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.00893

AC:

12948

AN:

1449900

Hom.:

714

Cov.:

AF XY:

0.00870

AC XY:

6280

AN XY:

721966

show subpopulations

African (AFR)

AF:

0.187

AC:

6220

AN:

33278

American (AMR)

AF:

0.0143

AC:

638

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

113

AN:

26072

East Asian (EAS)

AF:

0.0257

AC:

1018

AN:

39668

South Asian (SAS)

AF:

0.0199

AC:

1709

AN:

86074

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.0191

AC:

110

AN:

5754

European-Non Finnish (NFE)

AF:

0.00177

AC:

1949

AN:

1100930

Other (OTH)

AF:

0.0198

AC:

1186

AN:

60002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

567

1134

1701

2268

2835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0551

AC:

8378

AN:

152184

Hom.:

692

Cov.:

AF XY:

0.0539

AC XY:

4010

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.180

AC:

7488

AN:

41486

American (AMR)

AF:

0.0260

AC:

397

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.0191

AC:

AN:

5176

South Asian (SAS)

AF:

0.0191

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00246

AC:

167

AN:

68024

Other (OTH)

AF:

0.0473

AC:

100

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

347

695

1042

1390

1737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0218

Hom.:

361

Bravo

AF:

0.0620

Asia WGS

AF:

0.0530

AC:

182

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

(source)

DANN

Benign

0.48

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over