1-111239264-G-A

Variant names:

• chr1-111239264-G-A
• rs11583210
• NM_004000.3:c.918+332G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004000.3(CHI3L2):​c.918+332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 222,596 control chromosomes in the GnomAD database, including 6,732 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 0.23 (4275 hom., cov: 32)
  • Exomes 𝑓: 0.26 (2457 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004000.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	NM_004000.3	MANE Select	c.918+332G>A		intron	N/A	NP_003991.2
	CHI3L2	NM_001025197.1		c.888+332G>A		intron	N/A	NP_001020368.1
	CHI3L2	NM_001025199.2		c.681+332G>A		intron	N/A	NP_001020370.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.918+332G>A		intron	N/A	ENSP00000358763.4
	CHI3L2	ENST00000466741.5	TSL:1	c.681+332G>A		intron	N/A	ENSP00000437086.1
	CHI3L2	ENST00000445067.6	TSL:5	c.918+332G>A		intron	N/A	ENSP00000437082.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34484 AN: 152020 Hom.: 4274 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.255 AC: 17994 AN: 70458 Hom.: 2457 Cov.: 0 AF XY: 0.260 AC XY: 9175 AN XY: 35276

African (AFR) AF: 0.145 AC: 263 AN: 1818

American (AMR) AF: 0.326 AC: 513 AN: 1574

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 581 AN: 2574

East Asian (EAS) AF: 0.101 AC: 325 AN: 3204

South Asian (SAS) AF: 0.327 AC: 1288 AN: 3938

European-Finnish (FIN) AF: 0.205 AC: 824 AN: 4014

Middle Eastern (MID) AF: 0.276 AC: 118 AN: 428

European-Non Finnish (NFE) AF: 0.270 AC: 12908 AN: 47842

Other (OTH) AF: 0.232 AC: 1174 AN: 5066

GnomAD4 genome AF: 0.227 AC: 34515 AN: 152138 Hom.: 4275 Cov.: 32 AF XY: 0.226 AC XY: 16843 AN XY: 74388

African (AFR) AF: 0.143 AC: 5915 AN: 41500

American (AMR) AF: 0.294 AC: 4489 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3466

East Asian (EAS) AF: 0.0969 AC: 502 AN: 5182

South Asian (SAS) AF: 0.304 AC: 1464 AN: 4808

European-Finnish (FIN) AF: 0.197 AC: 2086 AN: 10602

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18469 AN: 67982

Other (OTH) AF: 0.214 AC: 453 AN: 2112

Alfa AF: 0.255 Hom.: 1183

Bravo AF: 0.229

Asia WGS AF: 0.192 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	18
DANN	Benign	0.79
PhyloP100		-0.96
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11583210; hg19: chr1-111781886;