rs11102221

Positions:

• chr1-111242194-G-A

Variant summary

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

The NM_004000.3(CHI3L2):​c.1036-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,612,402 control chromosomes in the GnomAD database, including 59,899 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.28 (6391 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53508 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476

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]

CHI3L2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.1036-33G>A		intron_variant		ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.1006-33G>A		intron_variant			NP_001020368.1
CHI3L2	NM_001025199.2	c.799-33G>A		intron_variant			NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.1036-33G>A		intron_variant		1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42982 AN: 151944 Hom.: 6372 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.262

GnomAD3 exomes AF: 0.279 AC: 70040 AN: 250864 Hom.: 10744 AF XY: 0.275 AC XY: 37315 AN XY: 135624

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.402

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.110

Gnomad SAS exome AF: 0.349

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.265 AC: 387363 AN: 1460340 Hom.: 53508 Cov.: 33 AF XY: 0.267 AC XY: 194044 AN XY: 726548

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.283 AC: 43069 AN: 152062 Hom.: 6391 Cov.: 32 AF XY: 0.282 AC XY: 20972 AN XY: 74332

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.263

Alfa AF: 0.261 Hom.: 9101

Bravo AF: 0.293

Asia WGS AF: 0.243 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.64
BranchPoint Hunter		1.0

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: rs11102221; hg19: chr1-111784816; COSMIC: COSV63874081; COSMIC: COSV63874081;