1-111229743-G-A

Variant names:

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

Variant summary

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

The ENST00000466741.5(CHI3L2):​c.-306G>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. 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: 29)
  • Exomes 𝑓: 0.0000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHI3L2 ENST00000466741.5 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: 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 (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.41-109G>A		intron_variant	Intron 1 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025199.2	c.-306G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 10		NP_001020370.1
CHI3L2	NM_001025199.2	c.-306G>A		5_prime_UTR_variant	Exon 1 of 10		NP_001020370.1
CHI3L2	NM_001025197.1	c.41-999G>A		intron_variant	Intron 1 of 9		NP_001020368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.41-109G>A		intron_variant	Intron 1 of 10	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000236 AC: 3 AN: 1269008 Hom.: 0 Cov.: 32 AF XY: 0.00000160 AC XY: 1 AN XY: 626796

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26926

American (AMR) AF: 0.00 AC: 0 AN: 31756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20072

East Asian (EAS) AF: 0.00 AC: 0 AN: 32916

South Asian (SAS) AF: 0.00 AC: 0 AN: 69974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4638

European-Non Finnish (NFE) AF: 0.00000304 AC: 3 AN: 986832

Other (OTH) AF: 0.00 AC: 0 AN: 50144

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0482410), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.7
DANN	Benign	0.78
PhyloP100		-0.28
PromoterAI		-0.052	Neutral

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;