chr1-111242194-G-A

Variant names:

• chr1-111242194-G-A
• rs11102221
• NM_004000.3:c.1036-33G>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.1036-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,612,402 control chromosomes in the GnomAD database, including 59,899 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.28 (6391 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53508 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 13 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 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.1036-33G>A		intron	N/A	NP_003991.2
	CHI3L2	NM_001025197.1		c.1006-33G>A		intron	N/A	NP_001020368.1
	CHI3L2	NM_001025199.2		c.799-33G>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.1036-33G>A		intron	N/A	ENSP00000358763.4
	CHI3L2	ENST00000466741.5	TSL:1	c.799-33G>A		intron	N/A	ENSP00000437086.1
	CHI3L2	ENST00000445067.6	TSL:5	c.1036-33G>A		intron	N/A	ENSP00000437082.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42982 AN: 151944 Hom.: 6372 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.279 AC: 70040 AN: 250864 AF XY: 0.275

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.402

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.110

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.265 AC: 387363 AN: 1460340 Hom.: 53508 Cov.: 33 AF XY: 0.267 AC XY: 194044 AN XY: 726548

African (AFR) AF: 0.343 AC: 11463 AN: 33426

American (AMR) AF: 0.389 AC: 17366 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5896 AN: 26114

East Asian (EAS) AF: 0.122 AC: 4824 AN: 39688

South Asian (SAS) AF: 0.351 AC: 30251 AN: 86194

European-Finnish (FIN) AF: 0.196 AC: 10460 AN: 53298

Middle Eastern (MID) AF: 0.267 AC: 1536 AN: 5754

European-Non Finnish (NFE) AF: 0.261 AC: 290164 AN: 1110862

Other (OTH) AF: 0.255 AC: 15403 AN: 60314

GnomAD4 genome AF: 0.283 AC: 43069 AN: 152062 Hom.: 6391 Cov.: 32 AF XY: 0.282 AC XY: 20972 AN XY: 74332

African (AFR) AF: 0.347 AC: 14380 AN: 41464

American (AMR) AF: 0.318 AC: 4856 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3470

East Asian (EAS) AF: 0.116 AC: 603 AN: 5184

South Asian (SAS) AF: 0.320 AC: 1538 AN: 4804

European-Finnish (FIN) AF: 0.194 AC: 2053 AN: 10556

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17918 AN: 67982

Other (OTH) AF: 0.263 AC: 557 AN: 2114

Alfa AF: 0.268 Hom.: 22066

Bravo AF: 0.293

Asia WGS AF: 0.243 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.64
PhyloP100		0.48
BranchPoint Hunter		1.0
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: rs11102221; hg19: chr1-111784816; COSMIC: COSV63874081; COSMIC: COSV63874081;