1-111236202-T-C

Variant summary

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

The NM_004000.3(CHI3L2):c.735+49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 1,599,128 control chromosomes in the GnomAD database, including 380,772 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 0.65 (32714 hom., cov: 31)
  • Exomes 𝑓: 0.69 (348058 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L2	NM_004000.3	c.735+49T>C		intron_variant		ENST00000369748.9
CHI3L2	NM_001025197.1	c.705+49T>C		intron_variant
CHI3L2	NM_001025199.2	c.498+49T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000369748.9	c.735+49T>C		intron_variant		1	NM_004000.3	P1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98929 AN: 151792 Hom.: 32676 Cov.: 31

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.640

GnomAD3 exomes AF: 0.682 AC: 162137 AN: 237566 Hom.: 55265 AF XY: 0.686 AC XY: 88540 AN XY: 129088

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.658

Gnomad ASJ exome AF: 0.613

Gnomad EAS exome AF: 0.661

Gnomad SAS exome AF: 0.745

Gnomad FIN exome AF: 0.702

Gnomad NFE exome AF: 0.696

Gnomad OTH exome AF: 0.673

GnomAD4 exome AF: 0.693 AC: 1002630 AN: 1447218 Hom.: 348058 Cov.: 27 AF XY: 0.694 AC XY: 499505 AN XY: 719572

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.743

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.681

GnomAD4 genome AF: 0.652 AC: 99022 AN: 151910 Hom.: 32714 Cov.: 31 AF XY: 0.653 AC XY: 48464 AN XY: 74268

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.639

Alfa AF: 0.674 Hom.: 58275

Bravo AF: 0.640

Asia WGS AF: 0.709 AC: 2464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.17
Dann	Benign	0.25

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: rs2251608; hg19: chr1-111778824;