NM_004000.3:c.*93C>A

Variant names:

• chr1-111243307-C-A
• rs8535
• NM_004000.3:c.*93C>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.*93C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 453,778 control chromosomes in the GnomAD database, including 17,622 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 0.24 (5094 hom., cov: 33)
  • Exomes 𝑓: 0.28 (12528 hom.)
• Consequence: CHI3L2 NM_004000.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 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.*93C>A		3_prime_UTR	Exon 11 of 11	NP_003991.2	Q15782-4
	CHI3L2	NM_001025197.1		c.*93C>A		3_prime_UTR	Exon 10 of 10	NP_001020368.1	Q15782-6
	CHI3L2	NM_001025199.2		c.*93C>A		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.*93C>A		3_prime_UTR	Exon 11 of 11	ENSP00000358763.4	Q15782-4
	CHI3L2	ENST00000466741.5	TSL:1	c.*93C>A		3_prime_UTR	Exon 10 of 10	ENSP00000437086.1	Q15782-5
	CHI3L2	ENST00000445067.6	TSL:5	c.*93C>A		3_prime_UTR	Exon 13 of 13	ENSP00000437082.1	Q15782-4

Frequencies

GnomAD3 genomes AF: 0.243 AC: 37024 AN: 152078 Hom.: 5087 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.283 AC: 85279 AN: 301582 Hom.: 12528 Cov.: 0 AF XY: 0.282 AC XY: 48343 AN XY: 171632

African (AFR) AF: 0.103 AC: 883 AN: 8542

American (AMR) AF: 0.309 AC: 8389 AN: 27144

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 4162 AN: 10674

East Asian (EAS) AF: 0.347 AC: 3182 AN: 9172

South Asian (SAS) AF: 0.253 AC: 15087 AN: 59538

European-Finnish (FIN) AF: 0.254 AC: 3131 AN: 12322

Middle Eastern (MID) AF: 0.375 AC: 977 AN: 2608

European-Non Finnish (NFE) AF: 0.289 AC: 45436 AN: 157472

Other (OTH) AF: 0.286 AC: 4032 AN: 14110

GnomAD4 genome AF: 0.243 AC: 37023 AN: 152196 Hom.: 5094 Cov.: 33 AF XY: 0.245 AC XY: 18195 AN XY: 74406

African (AFR) AF: 0.114 AC: 4751 AN: 41548

American (AMR) AF: 0.301 AC: 4599 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1255 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1686 AN: 5162

South Asian (SAS) AF: 0.244 AC: 1175 AN: 4822

European-Finnish (FIN) AF: 0.257 AC: 2716 AN: 10584

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19727 AN: 67996

Other (OTH) AF: 0.281 AC: 593 AN: 2110

Alfa AF: 0.140 Hom.: 257

Bravo AF: 0.244

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		-0.84
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: rs8535; hg19: chr1-111785929;