1-111240649-G-A

Variant names:

• chr1-111240649-G-A
• rs2477578
• NM_004000.3:c.919-678G>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.919-678G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,132 control chromosomes in the GnomAD database, including 6,143 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 0.27 (6143 hom., cov: 32)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004000.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	NM_004000.3	MANE Select	c.919-678G>A		intron	N/A	NP_003991.2
	CHI3L2	NM_001025197.1		c.889-678G>A		intron	N/A	NP_001020368.1
	CHI3L2	NM_001025199.2		c.682-678G>A		intron	N/A	NP_001020370.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.919-678G>A		intron	N/A	ENSP00000358763.4
	CHI3L2	ENST00000466741.5	TSL:1	c.682-678G>A		intron	N/A	ENSP00000437086.1
	CHI3L2	ENST00000445067.6	TSL:5	c.919-678G>A		intron	N/A	ENSP00000437082.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41684 AN: 152014 Hom.: 6146 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.274 AC: 41686 AN: 152132 Hom.: 6143 Cov.: 32 AF XY: 0.269 AC XY: 19997 AN XY: 74346

African (AFR) AF: 0.180 AC: 7462 AN: 41512

American (AMR) AF: 0.229 AC: 3506 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1230 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1033 AN: 5182

South Asian (SAS) AF: 0.239 AC: 1154 AN: 4822

European-Finnish (FIN) AF: 0.323 AC: 3405 AN: 10550

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23015 AN: 67986

Other (OTH) AF: 0.291 AC: 615 AN: 2110

Alfa AF: 0.225 Hom.: 776

Bravo AF: 0.261

Asia WGS AF: 0.245 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.65
PhyloP100		0.45
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: rs2477578; hg19: chr1-111783271; COSMIC: COSV63873714; COSMIC: COSV63873714;