rs8535

Positions:

• chr1-111243307-C-A
• chr1-111243307-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.*93C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 453,778 control chromosomes in the GnomAD database, including 17,622 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 0.24 (5094 hom., cov: 33)
  • Exomes 𝑓: 0.28 (12528 hom.)
• Consequence: CHI3L2 NM_004000.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.*93C>A		3_prime_UTR_variant	11/11	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.*93C>A		3_prime_UTR_variant	10/10		NP_001020368.1
CHI3L2	NM_001025199.2	c.*93C>A		3_prime_UTR_variant	10/10		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.*93C>A		3_prime_UTR_variant	11/11	1	NM_004000.3	ENSP00000358763	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 37024 AN: 152078 Hom.: 5087 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.283 AC: 85279 AN: 301582 Hom.: 12528 Cov.: 0 AF XY: 0.282 AC XY: 48343 AN XY: 171632

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.347

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.243 AC: 37023 AN: 152196 Hom.: 5094 Cov.: 33 AF XY: 0.245 AC XY: 18195 AN XY: 74406

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.281

Alfa AF: 0.140 Hom.: 257

Bravo AF: 0.244

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.72

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: rs8535; hg19: chr1-111785929;