rs2182115

Positions:

• chr1-111231515-C-G
• chr1-111231515-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004000.3(CHI3L2):​c.329+221C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 448,354 control chromosomes in the GnomAD database, including 2,899 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 0.093 (790 hom., cov: 33)
  • Exomes 𝑓: 0.11 (2109 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L2	NM_004000.3	c.329+221C>G		intron_variant		ENST00000369748.9
CHI3L2	NM_001025197.1	c.299+221C>G		intron_variant
CHI3L2	NM_001025199.2	c.92+221C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000369748.9	c.329+221C>G		intron_variant		1	NM_004000.3	P1

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14100 AN: 152172 Hom.: 791 Cov.: 33

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.109 AC: 32267 AN: 296064 Hom.: 2109 Cov.: 2 AF XY: 0.111 AC XY: 16951 AN XY: 152578

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.0646

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.00100

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0926 AC: 14101 AN: 152290 Hom.: 790 Cov.: 33 AF XY: 0.0936 AC XY: 6968 AN XY: 74460

Gnomad4 AFR AF: 0.0394

Gnomad4 AMR AF: 0.0831

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0480 Hom.: 53

Bravo AF: 0.0866

Asia WGS AF: 0.0820 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs2182115; hg19: chr1-111774137;