1-111241536-T-C

Variant names:

• chr1-111241536-T-C
• rs942693
• NM_004000.3:c.1035+93T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004000.3(CHI3L2):​c.1035+93T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 713,402 control chromosomes in the GnomAD database, including 31,506 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 (5579 hom., cov: 32)
  • Exomes 𝑓: 0.30 (25927 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	NM_004000.3	MANE Select	c.1035+93T>C		intron	N/A	NP_003991.2	Q15782-4
	CHI3L2	NM_001025197.1		c.1005+93T>C		intron	N/A	NP_001020368.1	Q15782-6
	CHI3L2	NM_001025199.2		c.798+93T>C		intron	N/A	NP_001020370.1	Q15782-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.1035+93T>C		intron	N/A	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.798+93T>C		intron	N/A	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000445067.6	TSL:5	c.1035+93T>C		intron	N/A	ENSP00000437082.1	Q15782-4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37908 AN: 151982 Hom.: 5584 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.296 AC: 166211 AN: 561304 Hom.: 25927 AF XY: 0.295 AC XY: 87798 AN XY: 297824

African (AFR) AF: 0.0944 AC: 1462 AN: 15480

American (AMR) AF: 0.163 AC: 4494 AN: 27520

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 4995 AN: 15108

East Asian (EAS) AF: 0.172 AC: 5934 AN: 34448

South Asian (SAS) AF: 0.224 AC: 11728 AN: 52402

European-Finnish (FIN) AF: 0.341 AC: 16007 AN: 46966

Middle Eastern (MID) AF: 0.271 AC: 1004 AN: 3700

European-Non Finnish (NFE) AF: 0.332 AC: 111429 AN: 335862

Other (OTH) AF: 0.307 AC: 9158 AN: 29818

GnomAD4 genome AF: 0.249 AC: 37900 AN: 152098 Hom.: 5579 Cov.: 32 AF XY: 0.245 AC XY: 18230 AN XY: 74342

African (AFR) AF: 0.0967 AC: 4014 AN: 41510

American (AMR) AF: 0.215 AC: 3289 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5176

South Asian (SAS) AF: 0.239 AC: 1149 AN: 4816

European-Finnish (FIN) AF: 0.321 AC: 3393 AN: 10558

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22976 AN: 67970

Other (OTH) AF: 0.276 AC: 582 AN: 2108

Alfa AF: 0.302 Hom.: 11253

Bravo AF: 0.233

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.5
DANN	Benign	0.75
PhyloP100		0.088
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs942693; hg19: chr1-111784158;