1-111315301-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_201653.4(CHIA):​c.346C>T​(p.Arg116Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,612,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

CHIA
NM_201653.4 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

Publications

1 publications found
Variant links:
Genes affected
CHIA (HGNC:17432): (chitinase acidic) The protein encoded by this gene degrades chitin, which is found in the cell wall of most fungi as well as in arthropods and some nematodes. The encoded protein can also stimulate interleukin 13 expression, and variations in this gene can lead to asthma susceptibility. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.942

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHIANM_201653.4 linkc.346C>T p.Arg116Cys missense_variant Exon 6 of 12 ENST00000369740.6 NP_970615.2 Q9BZP6-1A8K3T7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHIAENST00000369740.6 linkc.346C>T p.Arg116Cys missense_variant Exon 6 of 12 1 NM_201653.4 ENSP00000358755.1 Q9BZP6-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152096
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000479
GnomAD2 exomes
AF:
0.0000318
AC:
8
AN:
251342
AF XY:
0.0000368
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000315
AC:
46
AN:
1460538
Hom.:
0
Cov.:
30
AF XY:
0.0000427
AC XY:
31
AN XY:
726602
show subpopulations
African (AFR)
AF:
0.0000598
AC:
2
AN:
33442
American (AMR)
AF:
0.0000671
AC:
3
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39700
South Asian (SAS)
AF:
0.000244
AC:
21
AN:
86206
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4740
European-Non Finnish (NFE)
AF:
0.0000162
AC:
18
AN:
1111892
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60280
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152214
Hom.:
0
Cov.:
31
AF XY:
0.0000537
AC XY:
4
AN XY:
74420
show subpopulations
African (AFR)
AF:
0.0000722
AC:
3
AN:
41540
American (AMR)
AF:
0.000131
AC:
2
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5166
South Asian (SAS)
AF:
0.000208
AC:
1
AN:
4814
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68006
Other (OTH)
AF:
0.000474
AC:
1
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 13, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.346C>T (p.R116C) alteration is located in exon 6 (coding exon 5) of the CHIA gene. This alteration results from a C to T substitution at nucleotide position 346, causing the arginine (R) at amino acid position 116 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Uncertain
0.020
T
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.44
.;T;T;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.93
D;.;D;D
M_CAP
Benign
0.027
D
MetaRNN
Pathogenic
0.94
D;D;D;D
MetaSVM
Benign
-0.95
T
MutationAssessor
Pathogenic
4.0
.;H;H;.
PhyloP100
1.5
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-6.4
D;D;D;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.013
D;D;D;D
Sift4G
Uncertain
0.020
D;D;D;D
Polyphen
0.94
.;P;P;.
Vest4
0.81, 0.81, 0.76
MutPred
0.95
.;Loss of disorder (P = 0.0242);Loss of disorder (P = 0.0242);.;
MVP
0.43
MPC
0.15
ClinPred
0.76
D
GERP RS
3.8
Varity_R
0.78
gMVP
0.87
Mutation Taster
=30/70
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs543573136; hg19: chr1-111857923; API