1-111241360-C-T

Variant names:

• chr1-111241360-C-T
• rs13721
• NM_004000.3:c.952C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004000.3(CHI3L2):​c.952C>T​(p.Arg318Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,596,686 control chromosomes in the GnomAD database, including 17,974 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1314 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16660 hom.)
• Consequence: CHI3L2 NM_004000.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.490
• Publications: 23 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004617125).
• BP6: Variant 1-111241360-C-T is Benign according to our data. Variant chr1-111241360-C-T is described in ClinVar as Benign. ClinVar VariationId is 402537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHI3L2	NM_004000.3	c.952C>T	p.Arg318Trp	missense_variant	Exon 9 of 11	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1	c.922C>T	p.Arg308Trp	missense_variant	Exon 8 of 10		NP_001020368.1
CHI3L2	NM_001025199.2	c.715C>T	p.Arg239Trp	missense_variant	Exon 8 of 10		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9	c.952C>T	p.Arg318Trp	missense_variant	Exon 9 of 11	1	NM_004000.3	ENSP00000358763.4

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17172 AN: 151950 Hom.: 1311 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0914

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.0952

GnomAD2 exomes AF: 0.155 AC: 38846 AN: 251400 AF XY: 0.150

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.333

Gnomad ASJ exome AF: 0.0959

Gnomad EAS exome AF: 0.0880

Gnomad FIN exome AF: 0.0836

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.142 AC: 205734 AN: 1444618 Hom.: 16660 Cov.: 30 AF XY: 0.143 AC XY: 102805 AN XY: 719624

African (AFR) AF: 0.0211 AC: 704 AN: 33370

American (AMR) AF: 0.316 AC: 14110 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 2376 AN: 26034

East Asian (EAS) AF: 0.0935 AC: 3706 AN: 39654

South Asian (SAS) AF: 0.170 AC: 14621 AN: 85944

European-Finnish (FIN) AF: 0.0868 AC: 4636 AN: 53408

Middle Eastern (MID) AF: 0.0728 AC: 418 AN: 5742

European-Non Finnish (NFE) AF: 0.144 AC: 157809 AN: 1095968

Other (OTH) AF: 0.123 AC: 7354 AN: 59810

GnomAD4 genome AF: 0.113 AC: 17182 AN: 152068 Hom.: 1314 Cov.: 32 AF XY: 0.113 AC XY: 8395 AN XY: 74326

African (AFR) AF: 0.0285 AC: 1184 AN: 41502

American (AMR) AF: 0.203 AC: 3110 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3470

East Asian (EAS) AF: 0.0916 AC: 473 AN: 5164

South Asian (SAS) AF: 0.153 AC: 736 AN: 4804

European-Finnish (FIN) AF: 0.0788 AC: 831 AN: 10550

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.149 AC: 10112 AN: 67976

Other (OTH) AF: 0.0947 AC: 200 AN: 2112

Alfa AF: 0.127 Hom.: 768

TwinsUK AF: 0.142 AC: 526

ALSPAC AF: 0.145 AC: 557

ExAC AF: 0.149 AC: 18147

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.54
DEOGEN2	Benign	0.0025	T;.;T;.;.;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.84	.;T;T;.;T;T;T
MetaRNN	Benign	0.0046	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.;N;.;.;.;.
PhyloP100		0.49
PrimateAI	Benign	0.31	T
PROVEAN	Benign	2.2	N;N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	1.0	T;T;T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T;T;T
Polyphen		1.0	D;.;D;.;.;.;.
Vest4		0.051
MPC		0.018
ClinPred		0.021	T
GERP RS		3.6
Varity_R		0.090
gMVP		0.35
Mutation Taster		=98/2	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: rs13721; hg19: chr1-111783982; COSMIC: COSV63873261; COSMIC: COSV63873261;