chr1-111235708-G-A

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

8
10

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]

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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 UniProt
CHI3L2NM_004000.3 linkuse as main transcriptc.550G>A p.Val184Ile missense_variant 6/11 ENST00000369748.9
CHI3L2NM_001025197.1 linkuse as main transcriptc.520G>A p.Val174Ile missense_variant 5/10
CHI3L2NM_001025199.2 linkuse as main transcriptc.313G>A p.Val105Ile missense_variant 5/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHI3L2ENST00000369748.9 linkuse as main transcriptc.550G>A p.Val184Ile missense_variant 6/111 NM_004000.3 P1Q15782-4

Frequencies

GnomAD3 genomes
AF:
0.00640
AC:
974
AN:
152242
Hom.:
7
Cov.:
33
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.:
4
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.:
7
Cov.:
35
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.:
7
Cov.:
33
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.:
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 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
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
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

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

Other links and lift over

dbSNP: rs34049547; hg19: chr1-111778330; API