1-111242845-C-T

Position:

• chr1-111242845-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004000.3(CHI3L2):​c.*3-372C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,082 control chromosomes in the GnomAD database, including 6,166 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 0.27 (6166 hom., cov: 31)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.03

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.*3-372C>T		intron_variant		ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.*3-372C>T		intron_variant			NP_001020368.1
CHI3L2	NM_001025199.2	c.*3-372C>T		intron_variant			NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.*3-372C>T		intron_variant		1	NM_004000.3	ENSP00000358763	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41736 AN: 151964 Hom.: 6169 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41738 AN: 152082 Hom.: 6166 Cov.: 31 AF XY: 0.269 AC XY: 20021 AN XY: 74348

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.291

Alfa AF: 0.326 Hom.: 13877

Bravo AF: 0.262

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.057
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs3934923; hg19: chr1-111785467; COSMIC: COSV63873740; COSMIC: COSV63873740;