Genetic Variant CHI3L2:c.-306G>T (chr1-111229743-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000466741.5(CHI3L2):c.-306G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,412,358 control chromosomes in the GnomAD database, including 1,165 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 0.054 ( 622 hom., cov: 29)

Exomes 𝑓: 0.0083 ( 543 hom. )

Consequence

CHI3L2
ENST00000466741.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.283

Publications

3 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3 link	c.41-109G>T	intron_variant	Intron 1 of 10	ENST00000369748.9	NP_003991.2	Q15782-4
CHI3L2	NM_001025199.2 link	c.-306G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 10		NP_001020370.1	Q15782-5
CHI3L2	NM_001025199.2 link	c.-306G>T	5_prime_UTR_variant	Exon 1 of 10		NP_001020370.1	Q15782-5
CHI3L2	NM_001025197.1 link	c.41-999G>T	intron_variant	Intron 1 of 9		NP_001020368.1	Q15782-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9 link	c.41-109G>T		intron_variant	Intron 1 of 10	1	NM_004000.3	ENSP00000358763.4		Q15782-4

Frequencies

GnomAD3 genomes

AF:

0.0535

AC:

7667

AN:

143434

Hom.:

616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0102

Gnomad AMR

AF:

0.0254

Gnomad ASJ

AF:

0.00418

Gnomad EAS

AF:

0.0192

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0372

Gnomad NFE

AF:

0.00247

Gnomad OTH

AF:

0.0449

GnomAD4 exome

AF:

0.00830

AC:

10531

AN:

1268854

Hom.:

543

Cov.:

AF XY:

0.00816

AC XY:

5113

AN XY:

626730

show subpopulations

African (AFR)

AF:

0.187

AC:

5019

AN:

26880

American (AMR)

AF:

0.0139

AC:

440

AN:

31744

Ashkenazi Jewish (ASJ)

AF:

0.00463

AC:

AN:

20072

East Asian (EAS)

AF:

0.0259

AC:

852

AN:

32898

South Asian (SAS)

AF:

0.0190

AC:

1330

AN:

69944

European-Finnish (FIN)

AF:

0.0000437

AC:

AN:

45748

Middle Eastern (MID)

AF:

0.0209

AC:

AN:

4638

European-Non Finnish (NFE)

AF:

0.00178

AC:

1758

AN:

986806

Other (OTH)

AF:

0.0188

AC:

940

AN:

50124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

417

834

1250

1667

2084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<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:

0.0537

AC:

7701

AN:

143504

Hom.:

622

Cov.:

AF XY:

0.0530

AC XY:

3683

AN XY:

69532

show subpopulations

African (AFR)

AF:

0.177

AC:

6869

AN:

38788

American (AMR)

AF:

0.0251

AC:

363

AN:

14442

Ashkenazi Jewish (ASJ)

AF:

0.00418

AC:

AN:

3350

East Asian (EAS)

AF:

0.0193

AC:

AN:

5030

South Asian (SAS)

AF:

0.0193

AC:

AN:

4460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9122

Middle Eastern (MID)

AF:

0.0401

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00247

AC:

161

AN:

65198

Other (OTH)

AF:

0.0466

AC:

AN:

1954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

280

560

841

1121

1401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0300

Hom.:

438

Bravo

AF:

0.0609

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.1

(source)

DANN

Benign

0.83

PhyloP100

-0.28

PromoterAI

-0.050

Neutral

(source)

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