rs2764546

Positions:

• chr1-111219860-G-A

Variant summary

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

The ENST00000445067.6(CHI3L2):​c.-156-6084G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,166 control chromosomes in the GnomAD database, including 5,439 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 0.24 (5439 hom., cov: 32)
• Consequence: CHI3L2 ENST00000445067.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000445067.6	c.-156-6084G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37242 AN: 152048 Hom.: 5441 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.245 AC: 37238 AN: 152166 Hom.: 5439 Cov.: 32 AF XY: 0.242 AC XY: 18017 AN XY: 74384

Gnomad4 AFR AF: 0.0905

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.263

Alfa AF: 0.315 Hom.: 6416

Bravo AF: 0.227

Asia WGS AF: 0.234 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.75

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: rs2764546; hg19: chr1-111762482; COSMIC: COSV71667006;