rs942694

Variant names:

• chr1-111241516-T-C
• rs942694
• NM_004000.3:c.1035+73T>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.1035+73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 794,358 control chromosomes in the GnomAD database, including 34,627 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 (5571 hom., cov: 31)
  • Exomes 𝑓: 0.29 (29056 hom.)
• Consequence: CHI3L2 NM_004000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.1035+73T>C		intron_variant	Intron 9 of 10	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.1005+73T>C		intron_variant	Intron 8 of 9		NP_001020368.1
CHI3L2	NM_001025199.2	c.798+73T>C		intron_variant	Intron 8 of 9		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.1035+73T>C		intron_variant	Intron 9 of 10	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37895 AN: 151922 Hom.: 5576 Cov.: 31

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.291 AC: 186893 AN: 642318 Hom.: 29056 AF XY: 0.291 AC XY: 99199 AN XY: 340862

African (AFR) AF: 0.0925 AC: 1617 AN: 17476

American (AMR) AF: 0.159 AC: 5386 AN: 33774

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 5508 AN: 16774

East Asian (EAS) AF: 0.172 AC: 6151 AN: 35658

South Asian (SAS) AF: 0.222 AC: 12947 AN: 58256

European-Finnish (FIN) AF: 0.341 AC: 16920 AN: 49686

Middle Eastern (MID) AF: 0.267 AC: 1071 AN: 4008

European-Non Finnish (NFE) AF: 0.323 AC: 127330 AN: 393924

Other (OTH) AF: 0.304 AC: 9963 AN: 32762

GnomAD4 genome AF: 0.249 AC: 37887 AN: 152040 Hom.: 5571 Cov.: 31 AF XY: 0.245 AC XY: 18232 AN XY: 74312

African (AFR) AF: 0.0968 AC: 4020 AN: 41512

American (AMR) AF: 0.215 AC: 3283 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3466

East Asian (EAS) AF: 0.199 AC: 1030 AN: 5172

South Asian (SAS) AF: 0.239 AC: 1151 AN: 4818

European-Finnish (FIN) AF: 0.322 AC: 3395 AN: 10544

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

European-Non Finnish (NFE) AF: 0.338 AC: 22963 AN: 67940

Other (OTH) AF: 0.275 AC: 579 AN: 2108

Alfa AF: 0.302 Hom.: 10015

Bravo AF: 0.233

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.57
PhyloP100		-0.038
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: rs942694; hg19: chr1-111784138; COSMIC: COSV63874753; COSMIC: COSV63874753;