Genetic Variant CHI3L2:c.272+35A>G (chr1-111230978-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.272+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 1,554,704 control chromosomes in the GnomAD database, including 10,175 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 0.096 ( 980 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9195 hom. )

Consequence

CHI3L2
NM_004000.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.919

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:

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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 (EAS) allele frequency at 95% confidence interval = 0.337 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	UniProt
CHI3L2	NM_004000.3	MANE Select	c.272+35A>G	intron	N/A	NP_003991.2	Q15782-4
CHI3L2	NM_001025197.1		c.242+35A>G	intron	N/A	NP_001020368.1	Q15782-6
CHI3L2	NM_001025199.2		c.35+35A>G	intron	N/A	NP_001020370.1	Q15782-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.272+35A>G	intron	N/A	ENSP00000358763.4	Q15782-4
CHI3L2	ENST00000466741.5	TSL:1	c.35+35A>G	intron	N/A	ENSP00000437086.1	Q15782-5
CHI3L2	ENST00000445067.6	TSL:5	c.272+35A>G	intron	N/A	ENSP00000437082.1	Q15782-4

Frequencies

GnomAD3 genomes

AF:

0.0965

AC:

14672

AN:

152058

Hom.:

986

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0560

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0851

Gnomad OTH

AF:

0.0837

GnomAD2 exomes

AF:

0.120

AC:

28834

AN:

241226

AF XY:

0.120

show subpopulations

Gnomad AFR exome

AF:

0.0557

Gnomad AMR exome

AF:

0.0983

Gnomad ASJ exome

AF:

0.0421

Gnomad EAS exome

AF:

0.358

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.0841

Gnomad OTH exome

AF:

0.0917

GnomAD4 exome

AF:

0.100

AC:

140199

AN:

1402528

Hom.:

9195

Cov.:

AF XY:

0.101

AC XY:

70663

AN XY:

700054

show subpopulations

African (AFR)

AF:

0.0501

AC:

1625

AN:

32448

American (AMR)

AF:

0.0992

AC:

4348

AN:

43840

Ashkenazi Jewish (ASJ)

AF:

0.0400

AC:

1028

AN:

25684

East Asian (EAS)

AF:

0.366

AC:

14361

AN:

39290

South Asian (SAS)

AF:

0.157

AC:

13255

AN:

84430

European-Finnish (FIN)

AF:

0.159

AC:

8441

AN:

53052

Middle Eastern (MID)

AF:

0.0418

AC:

237

AN:

5668

European-Non Finnish (NFE)

AF:

0.0861

AC:

91293

AN:

1059720

Other (OTH)

AF:

0.0961

AC:

5611

AN:

58396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

6451

12902

19352

25803

32254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3532

7064

10596

14128

17660

<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:

0.0965

AC:

14678

AN:

152176

Hom.:

980

Cov.:

AF XY:

0.103

AC XY:

7666

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0561

AC:

2331

AN:

41540

American (AMR)

AF:

0.107

AC:

1633

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3468

East Asian (EAS)

AF:

0.350

AC:

1809

AN:

5164

South Asian (SAS)

AF:

0.183

AC:

879

AN:

4816

European-Finnish (FIN)

AF:

0.175

AC:

1856

AN:

10584

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0851

AC:

5785

AN:

67998

Other (OTH)

AF:

0.0838

AC:

177

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

667

1335

2002

2670

3337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0790

Hom.:

952

Bravo

AF:

0.0890

Asia WGS

AF:

0.221

AC:

769

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

(source)

DANN

Benign

0.46

PhyloP100

-0.92

PromoterAI

0.011

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over