1-111230946-G-C

Position:

• chr1-111230946-G-C

Variant summary

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

The ENST00000369748.9(CHI3L2):​c.272+3G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,610,816 control chromosomes in the GnomAD database, including 158,389 homozygotes. In-silico tool predicts 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.

• Frequency:
  • Genomes: 𝑓 0.40 (12783 hom., cov: 31)
  • Exomes 𝑓: 0.44 (145606 hom.)
• Consequence: CHI3L2 ENST00000369748.9 splice_region, intron
• Scores: Splicing: ADA: 0.09763
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

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]

CHI3L2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.272+3G>C		splice_region_variant, intron_variant		ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.242+3G>C		splice_region_variant, intron_variant			NP_001020368.1
CHI3L2	NM_001025199.2	c.35+3G>C		splice_region_variant, intron_variant			NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.272+3G>C		splice_region_variant, intron_variant		1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60856 AN: 151896 Hom.: 12788 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.401

GnomAD3 exomes AF: 0.424 AC: 105676 AN: 249460 Hom.: 23155 AF XY: 0.430 AC XY: 57986 AN XY: 134816

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.385

Gnomad EAS exome AF: 0.544

Gnomad SAS exome AF: 0.426

Gnomad FIN exome AF: 0.550

Gnomad NFE exome AF: 0.448

Gnomad OTH exome AF: 0.428

GnomAD4 exome AF: 0.443 AC: 646561 AN: 1458802 Hom.: 145606 Cov.: 32 AF XY: 0.443 AC XY: 321667 AN XY: 725706

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.541

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.400 AC: 60861 AN: 152014 Hom.: 12783 Cov.: 31 AF XY: 0.403 AC XY: 29926 AN XY: 74290

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.400

Alfa AF: 0.422 Hom.: 4504

Bravo AF: 0.380

Asia WGS AF: 0.485 AC: 1688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	18
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.098
dbscSNV1_RF	Benign	0.28
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.37		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2255089; hg19: chr1-111773568; COSMIC: COSV63873670; COSMIC: COSV63873670;