rs7542034

Positions:

• chr1-111241359-G-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.951G>A​(p.Thr317=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,602,084 control chromosomes in the GnomAD database, including 1,406 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 0.055 (692 hom., cov: 32)
  • Exomes 𝑓: 0.0089 (714 hom.)
• Consequence: CHI3L2 NM_004000.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

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=-0.85).
• BP7: Synonymous conserved (PhyloP=-3.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.951G>A	p.Thr317=	synonymous_variant	9/11	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.921G>A	p.Thr307=	synonymous_variant	8/10		NP_001020368.1
CHI3L2	NM_001025199.2	c.714G>A	p.Thr238=	synonymous_variant	8/10		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.951G>A	p.Thr317=	synonymous_variant	9/11	1	NM_004000.3	ENSP00000358763	P1

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8325 AN: 152066 Hom.: 680 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.0459

GnomAD3 exomes AF: 0.0196 AC: 4929 AN: 251438 Hom.: 340 AF XY: 0.0164 AC XY: 2234 AN XY: 135888

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.00526

Gnomad EAS exome AF: 0.0182

Gnomad SAS exome AF: 0.0207

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00247

Gnomad OTH exome AF: 0.0143

GnomAD4 exome AF: 0.00893 AC: 12948 AN: 1449900 Hom.: 714 Cov.: 27 AF XY: 0.00870 AC XY: 6280 AN XY: 721966

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.00433

Gnomad4 EAS exome AF: 0.0257

Gnomad4 SAS exome AF: 0.0199

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.00177

Gnomad4 OTH exome AF: 0.0198

GnomAD4 genome AF: 0.0551 AC: 8378 AN: 152184 Hom.: 692 Cov.: 32 AF XY: 0.0539 AC XY: 4010 AN XY: 74416

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00246

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0163 Hom.: 195

Bravo AF: 0.0620

Asia WGS AF: 0.0530 AC: 182 AN: 3478

EpiCase AF: 0.00349

EpiControl AF: 0.00314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.48

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: rs7542034; hg19: chr1-111783981; COSMIC: COSV63874075; COSMIC: COSV63874075;