1-111312237-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_201653.4(CHIA):​c.103C>T​(p.Arg35Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,614,084 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R35Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.012 ( 33 hom., cov: 31)
Exomes 𝑓: 0.0013 ( 36 hom. )

Consequence

CHIA
NM_201653.4 missense

Scores

1
6
11

Clinical Significance

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

Conservation

PhyloP100: -0.111

Publications

3 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: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0059217513).
BP6
Variant 1-111312237-C-T is Benign according to our data. Variant chr1-111312237-C-T is described in ClinVar as [Benign]. Clinvar id is 769525.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 = 0.0125 (1901/152254) while in subpopulation AFR AF = 0.0437 (1813/41520). AF 95% confidence interval is 0.042. There are 33 homozygotes in GnomAd4. There are 861 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHIANM_201653.4 linkc.103C>T p.Arg35Trp missense_variant Exon 4 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.103C>T p.Arg35Trp missense_variant Exon 4 of 12 1 NM_201653.4 ENSP00000358755.1 Q9BZP6-1

Frequencies

GnomAD3 genomes
AF:
0.0124
AC:
1893
AN:
152136
Hom.:
33
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0436
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00406
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00813
GnomAD2 exomes
AF:
0.00307
AC:
765
AN:
249344
AF XY:
0.00212
show subpopulations
Gnomad AFR exome
AF:
0.0431
Gnomad AMR exome
AF:
0.00209
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000167
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.00116
GnomAD4 exome
AF:
0.00128
AC:
1878
AN:
1461830
Hom.:
36
Cov.:
33
AF XY:
0.00110
AC XY:
801
AN XY:
727226
show subpopulations
African (AFR)
AF:
0.0464
AC:
1553
AN:
33472
American (AMR)
AF:
0.00224
AC:
100
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.0000383
AC:
1
AN:
26136
East Asian (EAS)
AF:
0.0000504
AC:
2
AN:
39698
South Asian (SAS)
AF:
0.000104
AC:
9
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00208
AC:
12
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000387
AC:
43
AN:
1111966
Other (OTH)
AF:
0.00262
AC:
158
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.487
Heterozygous variant carriers
0
100
201
301
402
502
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
46
92
138
184
230
<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:
0.0125
AC:
1901
AN:
152254
Hom.:
33
Cov.:
31
AF XY:
0.0116
AC XY:
861
AN XY:
74442
show subpopulations
African (AFR)
AF:
0.0437
AC:
1813
AN:
41520
American (AMR)
AF:
0.00405
AC:
62
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.000103
AC:
7
AN:
68024
Other (OTH)
AF:
0.00805
AC:
17
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
84
168
251
335
419
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.00809
Hom.:
26
Bravo
AF:
0.0146
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0406
AC:
170
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00357
AC:
432
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jun 15, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
T;T
Eigen
Benign
-0.017
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.27
N
LIST_S2
Uncertain
0.96
.;D
MetaRNN
Benign
0.0059
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.4
M;M
PhyloP100
-0.11
PrimateAI
Benign
0.31
T
PROVEAN
Pathogenic
-5.6
D;D
REVEL
Benign
0.21
Sift
Uncertain
0.016
D;D
Sift4G
Uncertain
0.016
D;D
Polyphen
0.90
P;P
Vest4
0.67
MVP
0.45
MPC
0.12
ClinPred
0.086
T
GERP RS
-0.17
Varity_R
0.78
gMVP
0.89
Mutation Taster
=92/8
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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: rs61752461; hg19: chr1-111854859; COSMIC: COSV99056565; API