1-111235708-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004000.3(CHI3L2):c.550G>A(p.Val184Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,208 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0064 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00076 (7 hom.)
• Consequence: CHI3L2 NM_004000.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.82

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061335266).
• BP6: Variant 1-111235708-G-A is Benign according to our data. Variant chr1-111235708-G-A is described in ClinVar as [Benign]. Clinvar id is 769524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0064 (975/152360) while in subpopulation AFR AF= 0.0221 (918/41584). AF 95% confidence interval is 0.0209. There are 7 homozygotes in gnomad4. There are 463 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L2	NM_004000.3	c.550G>A	p.Val184Ile	missense_variant	6/11	ENST00000369748.9
CHI3L2	NM_001025197.1	c.520G>A	p.Val174Ile	missense_variant	5/10
CHI3L2	NM_001025199.2	c.313G>A	p.Val105Ile	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000369748.9	c.550G>A	p.Val184Ile	missense_variant	6/11	1	NM_004000.3	P1

Frequencies

GnomAD3 genomes AF: 0.00640 AC: 974 AN: 152242 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00192 AC: 482 AN: 251360 Hom.: 4 AF XY: 0.00136 AC XY: 185 AN XY: 135846

Gnomad AFR exome AF: 0.0242

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000763 AC: 1115 AN: 1461848 Hom.: 7 Cov.: 35 AF XY: 0.000652 AC XY: 474 AN XY: 727222

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000186

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00640 AC: 975 AN: 152360 Hom.: 7 Cov.: 33 AF XY: 0.00621 AC XY: 463 AN XY: 74514

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00124 Hom.: 2

Bravo AF: 0.00773

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0238 AC: 105

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00243 AC: 295

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.026	T;.;T;.;T;T;.;.;.;T;.;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.89	D
MetaRNN	Benign	0.0061	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;.;.;.;M;.;.;.;.;.;.;.
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.65	N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.023	D;D;D;D;D;D;D;D;D;T;D;D
Polyphen		0.99	D;.;.;.;D;.;.;.;.;.;.;.
Vest4		0.31
MVP		0.30
MPC		0.091
ClinPred		0.055	T
GERP RS		3.4
Varity_R		0.59
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs34049547; hg19: chr1-111778330;