1-111241362-G-A

Variant names:

• chr1-111241362-G-A
• NM_004000.3:c.954G>A
• CHI3L2 p.Arg318Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004000.3(CHI3L2):​c.954G>A​(p.Arg318Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHI3L2 NM_004000.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=1.53 with no splicing effect.

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.954G>A	p.Arg318Arg	synonymous	Exon 9 of 11	NP_003991.2	Q15782-4
	CHI3L2	NM_001025197.1		c.924G>A	p.Arg308Arg	synonymous	Exon 8 of 10	NP_001020368.1	Q15782-6
	CHI3L2	NM_001025199.2		c.717G>A	p.Arg239Arg	synonymous	Exon 8 of 10	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.954G>A	p.Arg318Arg	synonymous	Exon 9 of 11	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.717G>A	p.Arg239Arg	synonymous	Exon 8 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000445067.6	TSL:5	c.954G>A	p.Arg318Arg	synonymous	Exon 11 of 13	ENSP00000437082.1	Q15782-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1454444 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724030

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105046

Other (OTH) AF: 0.00 AC: 0 AN: 60164

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.47
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-111783984;