rs942694

Positions:

• chr1-111241516-T-C

Variant summary

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

The NM_004000.3(CHI3L2):​c.1035+73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 794,358 control chromosomes in the GnomAD database, including 34,627 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 0.25 (5571 hom., cov: 31)
  • Exomes 𝑓: 0.29 (29056 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.1035+73T>C		intron_variant		ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.1005+73T>C		intron_variant			NP_001020368.1
CHI3L2	NM_001025199.2	c.798+73T>C		intron_variant			NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.1035+73T>C		intron_variant		1	NM_004000.3	ENSP00000358763	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37895 AN: 151922 Hom.: 5576 Cov.: 31

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.291 AC: 186893 AN: 642318 Hom.: 29056 AF XY: 0.291 AC XY: 99199 AN XY: 340862

Gnomad4 AFR exome AF: 0.0925

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.249 AC: 37887 AN: 152040 Hom.: 5571 Cov.: 31 AF XY: 0.245 AC XY: 18232 AN XY: 74312

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.275

Alfa AF: 0.280 Hom.: 1091

Bravo AF: 0.233

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.57

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: rs942694; hg19: chr1-111784138; COSMIC: COSV63874753; COSMIC: COSV63874753;