chr1-111243308-T-C

Variant names:

• chr1-111243308-T-C
• rs1056825
• NM_004000.3:c.*94T>C

Variant summary

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

The NM_004000.3(CHI3L2):​c.*94T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 453,450 control chromosomes in the GnomAD database, including 94,839 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 0.56 (26493 hom., cov: 32)
  • Exomes 𝑓: 0.67 (68346 hom.)
• Consequence: CHI3L2 NM_004000.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.706 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	NM_004000.3	MANE Select	c.*94T>C		3_prime_UTR	Exon 11 of 11	NP_003991.2	Q15782-4
	CHI3L2	NM_001025197.1		c.*94T>C		3_prime_UTR	Exon 10 of 10	NP_001020368.1	Q15782-6
	CHI3L2	NM_001025199.2		c.*94T>C		3_prime_UTR	Exon 10 of 10	NP_001020370.1	Q15782-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHI3L2	ENST00000369748.9	TSL:1 MANE Select	c.*94T>C		3_prime_UTR	Exon 11 of 11	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.*94T>C		3_prime_UTR	Exon 10 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000445067.6	TSL:5	c.*94T>C		3_prime_UTR	Exon 13 of 13	ENSP00000437082.1	Q15782-4

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85348 AN: 151964 Hom.: 26489 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.668 AC: 201412 AN: 301368 Hom.: 68346 Cov.: 0 AF XY: 0.674 AC XY: 115653 AN XY: 171472

African (AFR) AF: 0.274 AC: 2338 AN: 8548

American (AMR) AF: 0.631 AC: 17105 AN: 27114

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 6310 AN: 10652

East Asian (EAS) AF: 0.635 AC: 5824 AN: 9176

South Asian (SAS) AF: 0.715 AC: 42574 AN: 59554

European-Finnish (FIN) AF: 0.702 AC: 8650 AN: 12318

Middle Eastern (MID) AF: 0.573 AC: 1483 AN: 2588

European-Non Finnish (NFE) AF: 0.687 AC: 108062 AN: 157324

Other (OTH) AF: 0.643 AC: 9066 AN: 14094

GnomAD4 genome AF: 0.561 AC: 85374 AN: 152082 Hom.: 26493 Cov.: 32 AF XY: 0.565 AC XY: 41995 AN XY: 74350

African (AFR) AF: 0.273 AC: 11314 AN: 41482

American (AMR) AF: 0.609 AC: 9307 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2153 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3362 AN: 5168

South Asian (SAS) AF: 0.726 AC: 3501 AN: 4820

European-Finnish (FIN) AF: 0.693 AC: 7333 AN: 10582

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46555 AN: 67968

Other (OTH) AF: 0.569 AC: 1201 AN: 2110

Alfa AF: 0.601 Hom.: 6649

Bravo AF: 0.539

Asia WGS AF: 0.648 AC: 2255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.73
PhyloP100		0.35
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: rs1056825; hg19: chr1-111785930; COSMIC: COSV63873747; COSMIC: COSV63873747;