1-111230823-T-A

Variant names:

• chr1-111230823-T-A
• rs538439659
• ENST00000466741.5:c.-86T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001025199.2(CHI3L2):​c.-86T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CHI3L2 NM_001025199.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025199.2. 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.152T>A	p.Ile51Asn	missense	Exon 3 of 11	NP_003991.2	Q15782-4
	CHI3L2	NM_001025199.2		c.-86T>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001020370.1	Q15782-5
	CHI3L2	NM_001025197.1		c.122T>A	p.Ile41Asn	missense	Exon 2 of 10	NP_001020368.1	Q15782-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	ENST00000466741.5	TSL:1	c.-86T>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.152T>A	p.Ile51Asn	missense	Exon 3 of 11	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.-86T>A		5_prime_UTR	Exon 2 of 10	ENSP00000437086.1	Q15782-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		3.0
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.98	D
Vest4		0.43
MutPred		0.83		Gain of disorder (P = 0.0061)
MVP		0.16
MPC		0.10
ClinPred		0.98	D
GERP RS		-1.1
PromoterAI		0.0048	Neutral
Varity_R		0.93
gMVP		0.92
Mutation Taster		=95/5	polymorphism

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: rs538439659; hg19: chr1-111773445;