1-111242845-C-T

Variant names:

• chr1-111242845-C-T
• rs3934923
• NM_004000.3:c.*3-372C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.93).
• 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 rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.*3-372C>T		intron_variant	Intron 10 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.*3-372C>T		intron_variant	Intron 9 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.*3-372C>T		intron_variant	Intron 9 of 9		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.*3-372C>T		intron_variant	Intron 10 of 10	1	NM_004000.3	ENSP00000358763.4

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

African (AFR) AF: 0.180 AC: 7475 AN: 41492

American (AMR) AF: 0.229 AC: 3506 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1226 AN: 3466

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5172

South Asian (SAS) AF: 0.239 AC: 1152 AN: 4822

European-Finnish (FIN) AF: 0.322 AC: 3400 AN: 10564

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23071 AN: 67976

Other (OTH) AF: 0.291 AC: 612 AN: 2104

Alfa AF: 0.314 Hom.: 21188

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
PhyloP100		-5.0
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: rs3934923; hg19: chr1-111785467; COSMIC: COSV63873740; COSMIC: COSV63873740;