Variant 1-111235708-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.82

Variant links:

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]

CHI3L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHI3L2	NM_004000.3 linkuse as main transcript	c.550G>A	p.Val184Ile	missense_variant	6/11	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1 linkuse as main transcript	c.520G>A	p.Val174Ile	missense_variant	5/10		NP_001020368.1
CHI3L2	NM_001025199.2 linkuse as main transcript	c.313G>A	p.Val105Ile	missense_variant	5/10		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9 linkuse as main transcript	c.550G>A	p.Val184Ile	missense_variant	6/11	1	NM_004000.3	ENSP00000358763	P1	Q15782-4

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

974

AN:

152242

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00136

AC XY:

185

AN XY:

135846

show subpopulations

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.:

Cov.:

AF XY:

0.000652

AC XY:

474

AN XY:

727222

show subpopulations

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.:

Cov.:

AF XY:

0.00621

AC XY:

463

AN XY:

74514

show subpopulations

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.:

Bravo

AF:

0.00773

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00243

AC:

295

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.41

CADD

Benign

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

LIST_S2

Uncertain

0.91

.;D;D;D;D;D;.;D;D;D;D;D

MetaRNN

Benign

0.0061

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.;.;.;M;.;.;.;.;.;.;.

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Benign

0.43

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over