rs2494004

Variant names:

• chr1-111233053-C-T
• rs2494004
• NM_004000.3:c.329+1759C>T

Variant summary

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

The NM_004000.3(CHI3L2):​c.329+1759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,070 control chromosomes in the GnomAD database, including 5,598 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 (5598 hom., cov: 32)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• 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=-0.9).
• 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.329+1759C>T		intron_variant	Intron 4 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.299+1759C>T		intron_variant	Intron 3 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.92+1759C>T		intron_variant	Intron 3 of 9		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.329+1759C>T		intron_variant	Intron 4 of 10	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37991 AN: 151952 Hom.: 5603 Cov.: 32

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.250 AC: 37983 AN: 152070 Hom.: 5598 Cov.: 32 AF XY: 0.246 AC XY: 18277 AN XY: 74326

African (AFR) AF: 0.0971 AC: 4027 AN: 41492

American (AMR) AF: 0.216 AC: 3303 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3470

East Asian (EAS) AF: 0.200 AC: 1033 AN: 5176

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4824

European-Finnish (FIN) AF: 0.323 AC: 3408 AN: 10542

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

European-Non Finnish (NFE) AF: 0.339 AC: 23027 AN: 67954

Other (OTH) AF: 0.276 AC: 582 AN: 2112

Alfa AF: 0.281 Hom.: 1189

Bravo AF: 0.234

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	-0.90
CADD	Benign	1.7
DANN	Benign	0.29
PhyloP100		-0.12
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: rs2494004; hg19: chr1-111775675;