1-111241360-C-A

Position:

• chr1-111241360-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004000.3(CHI3L2):​c.952C>A​(p.Arg318=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,591,004 control chromosomes in the GnomAD database, including 79,171 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 (5586 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73585 hom.)
• Consequence: CHI3L2 NM_004000.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.952C>A	p.Arg318=	synonymous_variant	9/11	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.922C>A	p.Arg308=	synonymous_variant	8/10		NP_001020368.1
CHI3L2	NM_001025199.2	c.715C>A	p.Arg239=	synonymous_variant	8/10		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.952C>A	p.Arg318=	synonymous_variant	9/11	1	NM_004000.3	ENSP00000358763	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37933 AN: 151932 Hom.: 5591 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.277

GnomAD3 exomes AF: 0.272 AC: 68285 AN: 251400 Hom.: 10241 AF XY: 0.280 AC XY: 38010 AN XY: 135878

Gnomad AFR exome AF: 0.0901

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.187

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.340

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.312 AC: 448265 AN: 1438954 Hom.: 73585 Cov.: 30 AF XY: 0.311 AC XY: 222930 AN XY: 717124

Gnomad4 AFR exome AF: 0.0904

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.249 AC: 37925 AN: 152050 Hom.: 5586 Cov.: 32 AF XY: 0.246 AC XY: 18254 AN XY: 74316

Gnomad4 AFR AF: 0.0967

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.276

Alfa AF: 0.248 Hom.: 768

EpiCase AF: 0.338

EpiControl AF: 0.344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.8
DANN	Benign	0.55

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: rs13721; hg19: chr1-111783982; COSMIC: COSV63873358; COSMIC: COSV63873358;