1-111229743-G-T

Variant names:

• chr1-111229743-G-T
• rs12070867
• ENST00000466741.5:c.-306G>T

Variant summary

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

The NM_001025199.2(CHI3L2):​c.-306G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,412,358 control chromosomes in the GnomAD database, including 1,165 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 0.054 (622 hom., cov: 29)
  • Exomes 𝑓: 0.0083 (543 hom.)
• Consequence: CHI3L2 NM_001025199.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

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.41-109G>T		intron	N/A	NP_003991.2	Q15782-4
	CHI3L2	NM_001025199.2		c.-306G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001020370.1	Q15782-5
	CHI3L2	NM_001025199.2		c.-306G>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	ENST00000466741.5	TSL:1	c.-306G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000466741.5	TSL:1	c.-306G>T		5_prime_UTR	Exon 1 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.41-109G>T		intron	N/A	ENSP00000358763.4	Q15782-4

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 7667 AN: 143434 Hom.: 616 Cov.: 29

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0102

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.00418

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0372

Gnomad NFE AF: 0.00247

Gnomad OTH AF: 0.0449

GnomAD4 exome AF: 0.00830 AC: 10531 AN: 1268854 Hom.: 543 Cov.: 32 AF XY: 0.00816 AC XY: 5113 AN XY: 626730

African (AFR) AF: 0.187 AC: 5019 AN: 26880

American (AMR) AF: 0.0139 AC: 440 AN: 31744

Ashkenazi Jewish (ASJ) AF: 0.00463 AC: 93 AN: 20072

East Asian (EAS) AF: 0.0259 AC: 852 AN: 32898

South Asian (SAS) AF: 0.0190 AC: 1330 AN: 69944

European-Finnish (FIN) AF: 0.0000437 AC: 2 AN: 45748

Middle Eastern (MID) AF: 0.0209 AC: 97 AN: 4638

European-Non Finnish (NFE) AF: 0.00178 AC: 1758 AN: 986806

Other (OTH) AF: 0.0188 AC: 940 AN: 50124

GnomAD4 genome AF: 0.0537 AC: 7701 AN: 143504 Hom.: 622 Cov.: 29 AF XY: 0.0530 AC XY: 3683 AN XY: 69532

African (AFR) AF: 0.177 AC: 6869 AN: 38788

American (AMR) AF: 0.0251 AC: 363 AN: 14442

Ashkenazi Jewish (ASJ) AF: 0.00418 AC: 14 AN: 3350

East Asian (EAS) AF: 0.0193 AC: 97 AN: 5030

South Asian (SAS) AF: 0.0193 AC: 86 AN: 4460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9122

Middle Eastern (MID) AF: 0.0401 AC: 11 AN: 274

European-Non Finnish (NFE) AF: 0.00247 AC: 161 AN: 65198

Other (OTH) AF: 0.0466 AC: 91 AN: 1954

Alfa AF: 0.0300 Hom.: 438

Bravo AF: 0.0609

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.1
DANN	Benign	0.83
PhyloP100		-0.28
PromoterAI		-0.050	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12070867; hg19: chr1-111772365;