rs2494006

Variant names:

• chr1-111240819-G-A
• rs2494006
• NM_004000.3:c.919-508G>A

Variant summary

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

The NM_004000.3(CHI3L2):​c.919-508G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,080 control chromosomes in the GnomAD database, including 5,586 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 0.25 (5586 hom., cov: 32)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.919-508G>A		intron_variant	Intron 8 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.889-508G>A		intron_variant	Intron 7 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.682-508G>A		intron_variant	Intron 7 of 9		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.919-508G>A		intron_variant	Intron 8 of 10	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37931 AN: 151962 Hom.: 5591 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.249 AC: 37923 AN: 152080 Hom.: 5586 Cov.: 32 AF XY: 0.246 AC XY: 18253 AN XY: 74328

African (AFR) AF: 0.0966 AC: 4009 AN: 41492

American (AMR) AF: 0.215 AC: 3296 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1029 AN: 5176

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4814

European-Finnish (FIN) AF: 0.323 AC: 3404 AN: 10554

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22986 AN: 67958

Other (OTH) AF: 0.276 AC: 583 AN: 2112

Alfa AF: 0.290 Hom.: 936

Bravo AF: 0.233

Asia WGS AF: 0.238 AC: 828 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	0.90
DANN	Benign	0.46
PhyloP100		-0.46
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: rs2494006; hg19: chr1-111783441; COSMIC: COSV63873722; COSMIC: COSV63873722;