NM_004000.3:c.272+3G>C

Variant names:

• chr1-111230946-G-C
• rs2255089
• NM_004000.3:c.272+3G>C

Variant summary

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

The NM_004000.3(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 NM_004000.3 splice_region, intron
• Scores: Splicing: ADA: 0.09763
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 14 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 (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.272+3G>C		splice_region_variant, intron_variant	Intron 3 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.242+3G>C		splice_region_variant, intron_variant	Intron 2 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.35+3G>C		splice_region_variant, intron_variant	Intron 2 of 9		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.272+3G>C		splice_region_variant, intron_variant	Intron 3 of 10	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

GnomAD2 exomes AF: 0.424 AC: 105676 AN: 249460 AF XY: 0.430

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 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

African (AFR) AF: 0.274 AC: 9156 AN: 33434

American (AMR) AF: 0.289 AC: 12897 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 10052 AN: 26104

East Asian (EAS) AF: 0.541 AC: 21469 AN: 39670

South Asian (SAS) AF: 0.422 AC: 36347 AN: 86098

European-Finnish (FIN) AF: 0.547 AC: 29167 AN: 53322

Middle Eastern (MID) AF: 0.353 AC: 2036 AN: 5764

European-Non Finnish (NFE) AF: 0.449 AC: 498697 AN: 1109486

Other (OTH) AF: 0.444 AC: 26740 AN: 60290

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

African (AFR) AF: 0.282 AC: 11697 AN: 41440

American (AMR) AF: 0.353 AC: 5386 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1379 AN: 3464

East Asian (EAS) AF: 0.552 AC: 2855 AN: 5170

South Asian (SAS) AF: 0.457 AC: 2206 AN: 4828

European-Finnish (FIN) AF: 0.547 AC: 5775 AN: 10558

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30382 AN: 67960

Other (OTH) AF: 0.400 AC: 845 AN: 2112

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
PhyloP100		-2.4
PromoterAI		-0.17	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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