1-111235565-A-G

Position:

• chr1-111235565-A-G

Variant summary

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

The NM_004000.3(CHI3L2):​c.481-74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,506,452 control chromosomes in the GnomAD database, including 131,512 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 0.34 (10257 hom., cov: 32)
  • Exomes 𝑓: 0.42 (121255 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.481-74A>G		intron_variant		ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.451-74A>G		intron_variant			NP_001020368.1
CHI3L2	NM_001025199.2	c.244-74A>G		intron_variant			NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.481-74A>G		intron_variant		1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51758 AN: 152036 Hom.: 10267 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.417 AC: 565224 AN: 1354298 Hom.: 121255 AF XY: 0.417 AC XY: 279861 AN XY: 670570

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.413

GnomAD4 genome AF: 0.340 AC: 51751 AN: 152154 Hom.: 10257 Cov.: 32 AF XY: 0.344 AC XY: 25551 AN XY: 74378

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.358

Alfa AF: 0.392 Hom.: 7404

Bravo AF: 0.315

Asia WGS AF: 0.457 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.82

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: rs2251715; hg19: chr1-111778187; COSMIC: COSV63875227; COSMIC: COSV63875227;