1-111314575-G-A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_201653.4(CHIA):​c.293G>A​(p.Gly98Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,268 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: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CHIA
NM_201653.4 missense

Scores

9
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.80

Publications

0 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: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHIANM_201653.4 linkc.293G>A p.Gly98Asp missense_variant Exon 5 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.293G>A p.Gly98Asp missense_variant Exon 5 of 12 1 NM_201653.4 ENSP00000358755.1 Q9BZP6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461268
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726968
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33464
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26128
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86234
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111482
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60368
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
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
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 18, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.293G>A (p.G98D) alteration is located in exon 5 (coding exon 4) of the CHIA gene. This alteration results from a G to A substitution at nucleotide position 293, causing the glycine (G) at amino acid position 98 to be replaced by an aspartic acid (D). 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
Pathogenic
0.68
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.17
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.38
.;T;T
Eigen
Pathogenic
0.79
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;.;D
M_CAP
Benign
0.057
D
MetaRNN
Pathogenic
0.98
D;D;D
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Pathogenic
3.8
.;H;H
PhyloP100
6.8
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-5.8
D;D;D
REVEL
Uncertain
0.57
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.020
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.92
MutPred
0.95
.;Loss of MoRF binding (P = 0.2082);Loss of MoRF binding (P = 0.2082);
MVP
0.59
MPC
0.23
ClinPred
1.0
D
GERP RS
3.6
Varity_R
0.96
gMVP
0.97
Mutation Taster
=56/44
polymorphism

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

Other links and lift over

dbSNP: rs1266342181; hg19: chr1-111857197; API