dbSNP rs13721: CHI3L2:p.Arg318Arg (chr1-111241360-C-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.952C>A(p.Arg318Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,591,004 control chromosomes in the GnomAD database, including 79,171 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 0.25 ( 5586 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73585 hom. )

Consequence

CHI3L2
NM_004000.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.490

Publications

23 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=-0.63).

BP7

Synonymous conserved (PhyloP=0.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3 link	c.952C>A	p.Arg318Arg	synonymous_variant	Exon 9 of 11	ENST00000369748.9	NP_003991.2	Q15782-4
CHI3L2	NM_001025197.1 link	c.922C>A	p.Arg308Arg	synonymous_variant	Exon 8 of 10		NP_001020368.1	Q15782-6
CHI3L2	NM_001025199.2 link	c.715C>A	p.Arg239Arg	synonymous_variant	Exon 8 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.952C>A	p.Arg318Arg	synonymous_variant	Exon 9 of 11	1	NM_004000.3	ENSP00000358763.4		Q15782-4

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37933

AN:

151932

Hom.:

5591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0969

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.277

GnomAD2 exomes

AF:

0.272

AC:

68285

AN:

251400

AF XY:

0.280

show subpopulations

Gnomad AFR exome

AF:

0.0901

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.333

Gnomad EAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.312

AC:

448265

AN:

1438954

Hom.:

73585

Cov.:

AF XY:

0.311

AC XY:

222930

AN XY:

717124

show subpopulations

African (AFR)

AF:

0.0904

AC:

3013

AN:

33314

American (AMR)

AF:

0.158

AC:

7072

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

8738

AN:

25992

East Asian (EAS)

AF:

0.174

AC:

6902

AN:

39630

South Asian (SAS)

AF:

0.226

AC:

19372

AN:

85888

European-Finnish (FIN)

AF:

0.341

AC:

18193

AN:

53396

Middle Eastern (MID)

AF:

0.272

AC:

1557

AN:

5726

European-Non Finnish (NFE)

AF:

0.334

AC:

364819

AN:

1090706

Other (OTH)

AF:

0.312

AC:

18599

AN:

59620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

12367

24735

37102

49470

61837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11320

22640

33960

45280

56600

<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:

0.249

AC:

37925

AN:

152050

Hom.:

5586

Cov.:

AF XY:

0.246

AC XY:

18254

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0967

AC:

4012

AN:

41488

American (AMR)

AF:

0.215

AC:

3291

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1205

AN:

3470

East Asian (EAS)

AF:

0.200

AC:

1035

AN:

5168

South Asian (SAS)

AF:

0.239

AC:

1148

AN:

4802

European-Finnish (FIN)

AF:

0.322

AC:

3395

AN:

10542

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.338

AC:

22996

AN:

67982

Other (OTH)

AF:

0.276

AC:

583

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1372

2743

4115

5486

6858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.145

Hom.:

768

EpiCase

AF:

0.338

EpiControl

AF:

0.344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.8

(source)

DANN

Benign

0.55

PhyloP100

0.49

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