Genetic Variant CHI3L2:c.40+32T>G (chr1-111227801-T-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.40+32T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,606,608 control chromosomes in the GnomAD database, including 410,160 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 0.70 ( 37048 hom., cov: 32)

Exomes 𝑓: 0.72 ( 373112 hom. )

Consequence

CHI3L2
NM_004000.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.125

Publications

16 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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3 link	c.40+32T>G		intron_variant	Intron 1 of 10	ENST00000369748.9	NP_003991.2	Q15782-4
CHI3L2	NM_001025197.1 link	c.40+32T>G		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.40+32T>G		intron_variant	Intron 1 of 10	1	NM_004000.3	ENSP00000358763.4		Q15782-4

Frequencies

GnomAD3 genomes

AF:

0.697

AC:

105933

AN:

151966

Hom.:

37003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.662

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.759

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.719

Gnomad OTH

AF:

0.674

GnomAD2 exomes

AF:

0.707

AC:

177464

AN:

251138

AF XY:

0.708

show subpopulations

Gnomad AFR exome

AF:

0.663

Gnomad AMR exome

AF:

0.684

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.749

Gnomad NFE exome

AF:

0.716

Gnomad OTH exome

AF:

0.696

GnomAD4 exome

AF:

0.715

AC:

1040352

AN:

1454524

Hom.:

373112

Cov.:

AF XY:

0.716

AC XY:

518500

AN XY:

724168

show subpopulations

African (AFR)

AF:

0.653

AC:

21771

AN:

33358

American (AMR)

AF:

0.680

AC:

30395

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

16099

AN:

26092

East Asian (EAS)

AF:

0.662

AC:

26269

AN:

39658

South Asian (SAS)

AF:

0.753

AC:

64820

AN:

86078

European-Finnish (FIN)

AF:

0.747

AC:

39889

AN:

53396

Middle Eastern (MID)

AF:

0.611

AC:

3514

AN:

5752

European-Non Finnish (NFE)

AF:

0.719

AC:

795221

AN:

1105386

Other (OTH)

AF:

0.705

AC:

42374

AN:

60122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

13298

26596

39894

53192

66490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.697

AC:

106032

AN:

152084

Hom.:

37048

Cov.:

AF XY:

0.698

AC XY:

51884

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.662

AC:

27456

AN:

41450

American (AMR)

AF:

0.672

AC:

10285

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.637

AC:

2212

AN:

3472

East Asian (EAS)

AF:

0.668

AC:

3456

AN:

5176

South Asian (SAS)

AF:

0.760

AC:

3662

AN:

4820

European-Finnish (FIN)

AF:

0.747

AC:

7910

AN:

10588

Middle Eastern (MID)

AF:

0.579

AC:

169

AN:

292

European-Non Finnish (NFE)

AF:

0.719

AC:

48883

AN:

67962

Other (OTH)

AF:

0.673

AC:

1422

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1697

3394

5090

6787

8484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.700

Hom.:

63776

Bravo

AF:

0.686

Asia WGS

AF:

0.722

AC:

2509

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.9

(source)

DANN

Benign

0.60

PhyloP100

0.13

PromoterAI

-0.031

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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1-111227801-T-G

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