rs2764546

Variant names:

• chr1-111219860-G-A
• rs2764546
• ENST00000445067.6:c.-156-6084G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.85).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000445067.6	c.-156-6084G>A		intron_variant	Intron 1 of 12	5		ENSP00000437082.1

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

African (AFR) AF: 0.0905 AC: 3757 AN: 41532

American (AMR) AF: 0.211 AC: 3229 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1135 AN: 3472

East Asian (EAS) AF: 0.171 AC: 886 AN: 5190

South Asian (SAS) AF: 0.242 AC: 1163 AN: 4812

European-Finnish (FIN) AF: 0.347 AC: 3662 AN: 10568

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22527 AN: 67978

Other (OTH) AF: 0.263 AC: 554 AN: 2110

Alfa AF: 0.302 Hom.: 7770

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
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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