Genetic Variant CHI3L2:c.481-74A>G (chr1-111235565-A-G) – 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.481-74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,506,452 control chromosomes in the GnomAD database, including 131,512 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 0.34 ( 10257 hom., cov: 32)

Exomes 𝑓: 0.42 ( 121255 hom. )

Consequence

CHI3L2
NM_004000.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.269

Publications

11 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 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.481-74A>G	intron	N/A	NP_003991.2
CHI3L2	NM_001025197.1		c.451-74A>G	intron	N/A	NP_001020368.1
CHI3L2	NM_001025199.2		c.244-74A>G	intron	N/A	NP_001020370.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.481-74A>G	intron	N/A	ENSP00000358763.4
CHI3L2	ENST00000466741.5	TSL:1	c.244-74A>G	intron	N/A	ENSP00000437086.1
CHI3L2	ENST00000445067.6	TSL:5	c.481-74A>G	intron	N/A	ENSP00000437082.1

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51758

AN:

152036

Hom.:

10267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.417

AC:

565224

AN:

1354298

Hom.:

121255

AF XY:

0.417

AC XY:

279861

AN XY:

670570

show subpopulations

African (AFR)

AF:

0.120

AC:

3612

AN:

30186

American (AMR)

AF:

0.259

AC:

8477

AN:

32734

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

8110

AN:

21366

East Asian (EAS)

AF:

0.543

AC:

21034

AN:

38734

South Asian (SAS)

AF:

0.390

AC:

28272

AN:

72452

European-Finnish (FIN)

AF:

0.502

AC:

24459

AN:

48736

Middle Eastern (MID)

AF:

0.302

AC:

1180

AN:

3902

European-Non Finnish (NFE)

AF:

0.426

AC:

447031

AN:

1050330

Other (OTH)

AF:

0.413

AC:

23049

AN:

55858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

15491

30982

46472

61963

77454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13658

27316

40974

54632

68290

<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:

0.340

AC:

51751

AN:

152154

Hom.:

10257

Cov.:

AF XY:

0.344

AC XY:

25551

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.131

AC:

5439

AN:

41522

American (AMR)

AF:

0.318

AC:

4869

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1351

AN:

3470

East Asian (EAS)

AF:

0.555

AC:

2879

AN:

5190

South Asian (SAS)

AF:

0.424

AC:

2044

AN:

4824

European-Finnish (FIN)

AF:

0.499

AC:

5282

AN:

10586

Middle Eastern (MID)

AF:

0.325

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.424

AC:

28807

AN:

67964

Other (OTH)

AF:

0.358

AC:

755

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1625

3250

4874

6499

8124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.390

Hom.:

10075

Bravo

AF:

0.315

Asia WGS

AF:

0.457

AC:

1590

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.1

(source)

DANN

Benign

0.82

PhyloP100

-0.27

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