dbSNP rs961364: CHI3L2:c.605+83G>A (chr1-111235846-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004000.3(CHI3L2):c.605+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,573,172 control chromosomes in the GnomAD database, including 60,724 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 0.24 ( 4875 hom., cov: 33)

Exomes 𝑓: 0.28 ( 55849 hom. )

Consequence

CHI3L2
NM_004000.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.185

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004000.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHI3L2	NM_004000.3	MANE Select	c.605+83G>A	intron	N/A	NP_003991.2
CHI3L2	NM_001025197.1		c.575+83G>A	intron	N/A	NP_001020368.1
CHI3L2	NM_001025199.2		c.368+83G>A	intron	N/A	NP_001020370.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.605+83G>A	intron	N/A	ENSP00000358763.4
CHI3L2	ENST00000466741.5	TSL:1	c.368+83G>A	intron	N/A	ENSP00000437086.1
CHI3L2	ENST00000445067.6	TSL:5	c.605+83G>A	intron	N/A	ENSP00000437082.1

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36160

AN:

152052

Hom.:

4869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.437

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.281

GnomAD4 exome

AF:

0.278

AC:

394373

AN:

1421002

Hom.:

55849

Cov.:

AF XY:

0.278

AC XY:

195403

AN XY:

703618

show subpopulations

African (AFR)

AF:

0.106

AC:

3434

AN:

32516

American (AMR)

AF:

0.307

AC:

12946

AN:

42136

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

8994

AN:

23622

East Asian (EAS)

AF:

0.334

AC:

13171

AN:

39412

South Asian (SAS)

AF:

0.247

AC:

19616

AN:

79542

European-Finnish (FIN)

AF:

0.254

AC:

13216

AN:

51968

Middle Eastern (MID)

AF:

0.378

AC:

2114

AN:

5592

European-Non Finnish (NFE)

AF:

0.280

AC:

304536

AN:

1087448

Other (OTH)

AF:

0.278

AC:

16346

AN:

58766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

14528

29056

43585

58113

72641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10300

20600

30900

41200

51500

<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:

0.238

AC:

36158

AN:

152170

Hom.:

4875

Cov.:

AF XY:

0.239

AC XY:

17808

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.112

AC:

4668

AN:

41524

American (AMR)

AF:

0.297

AC:

4540

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1246

AN:

3472

East Asian (EAS)

AF:

0.326

AC:

1688

AN:

5184

South Asian (SAS)

AF:

0.240

AC:

1157

AN:

4816

European-Finnish (FIN)

AF:

0.254

AC:

2685

AN:

10578

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19070

AN:

67986

Other (OTH)

AF:

0.279

AC:

589

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1374

2748

4121

5495

6869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.279

Hom.:

8275

Bravo

AF:

0.238

Asia WGS

AF:

0.256

AC:

891

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.7

(source)

DANN

Benign

0.61

PhyloP100

0.18

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over