1-111229879-G-T

Variant names:

• chr1-111229879-G-T
• rs770072900
• NM_004000.3:c.68G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004000.3(CHI3L2):​c.68G>T​(p.Gly23Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/26 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G23E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CHI3L2 NM_004000.3 missense, splice_region
• Scores: Splicing: ADA: 0.00007621
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060562253).

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.68G>T	p.Gly23Val	missense splice_region	Exon 2 of 11	NP_003991.2	Q15782-4
	CHI3L2	NM_001025199.2		c.-170G>T		splice_region	Exon 1 of 10	NP_001020370.1	Q15782-5
	CHI3L2	NM_001025199.2		c.-170G>T		5_prime_UTR	Exon 1 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.68G>T	p.Gly23Val	missense splice_region	Exon 2 of 11	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.-170G>T		splice_region	Exon 1 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000466741.5	TSL:1	c.-170G>T		5_prime_UTR	Exon 1 of 10	ENSP00000437086.1	Q15782-5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251458 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461672 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000671 AC: 3 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111872

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.049
Sift	Benign	0.49	T
Sift4G	Benign	0.61	T
Polyphen		0.20	B
Vest4		0.18
MutPred		0.59		Loss of sheet (P = 0.0315)
MVP		0.27
MPC		0.016
ClinPred		0.056	T
GERP RS		-0.25
PromoterAI		0.013	Neutral
Varity_R		0.047
gMVP		0.59
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000076
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.63		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.63		Position offset: -2

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

Other links and lift over

dbSNP: rs770072900; hg19: chr1-111772501;