Genetic Variant CHI3L2:c.735+49T>C (chr1-111236202-T-C) – 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.735+49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 1,599,128 control chromosomes in the GnomAD database, including 380,772 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 0.65 ( 32714 hom., cov: 31)

Exomes 𝑓: 0.69 ( 348058 hom. )

Consequence

CHI3L2
NM_004000.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

10 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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3 link	c.735+49T>C	intron_variant	Intron 7 of 10	ENST00000369748.9	NP_003991.2	Q15782-4
CHI3L2	NM_001025197.1 link	c.705+49T>C	intron_variant	Intron 6 of 9		NP_001020368.1	Q15782-6
CHI3L2	NM_001025199.2 link	c.498+49T>C	intron_variant	Intron 6 of 9		NP_001020370.1	Q15782-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9 link	c.735+49T>C		intron_variant	Intron 7 of 10	1	NM_004000.3	ENSP00000358763.4		Q15782-4

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

98929

AN:

151792

Hom.:

32676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.555

Gnomad AMI

AF:

0.560

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.640

GnomAD2 exomes

AF:

0.682

AC:

162137

AN:

237566

AF XY:

0.686

show subpopulations

Gnomad AFR exome

AF:

0.558

Gnomad AMR exome

AF:

0.658

Gnomad ASJ exome

AF:

0.613

Gnomad EAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.696

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.693

AC:

1002630

AN:

1447218

Hom.:

348058

Cov.:

AF XY:

0.694

AC XY:

499505

AN XY:

719572

show subpopulations

African (AFR)

AF:

0.553

AC:

18302

AN:

33122

American (AMR)

AF:

0.654

AC:

28269

AN:

43252

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

15741

AN:

25668

East Asian (EAS)

AF:

0.667

AC:

26349

AN:

39530

South Asian (SAS)

AF:

0.743

AC:

63467

AN:

85466

European-Finnish (FIN)

AF:

0.700

AC:

37119

AN:

53048

Middle Eastern (MID)

AF:

0.594

AC:

3310

AN:

5572

European-Non Finnish (NFE)

AF:

0.698

AC:

769348

AN:

1101718

Other (OTH)

AF:

0.681

AC:

40725

AN:

59842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

14902

29804

44707

59609

74511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19498

38996

58494

77992

97490

<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:

0.652

AC:

99022

AN:

151910

Hom.:

32714

Cov.:

AF XY:

0.653

AC XY:

48464

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.555

AC:

22994

AN:

41404

American (AMR)

AF:

0.653

AC:

9970

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

2202

AN:

3470

East Asian (EAS)

AF:

0.673

AC:

3476

AN:

5168

South Asian (SAS)

AF:

0.750

AC:

3603

AN:

4806

European-Finnish (FIN)

AF:

0.696

AC:

7342

AN:

10550

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.698

AC:

47412

AN:

67934

Other (OTH)

AF:

0.639

AC:

1348

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1732

3464

5195

6927

8659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.675

Hom.:

132591

Bravo

AF:

0.640

Asia WGS

AF:

0.709

AC:

2464

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.17

(source)

DANN

Benign

0.25

PhyloP100

-1.1

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