1-111312237-C-T

Variant names:

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

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]

CHIA links:

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
CHIA	NM_201653.4 link	c.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
CHIA	ENST00000369740.6 link	c.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.:

Cov.:

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.:

Cov.:

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:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.000104

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000387

AC:

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

100

201

301

402

502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0125

AC:

1901

AN:

152254

Hom.:

Cov.:

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:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00805

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

168

251

335

419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00809

Hom.:

Bravo

AF:

0.0146

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0406

AC:

170

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00357

AC:

432

Asia WGS

AF:

0.00173

AC:

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

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

-0.017

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.96

.;D

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

-0.11

PrimateAI

Benign

0.31

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

GERP RS

-0.17

Varity_R

0.78

gMVP

0.89

Mutation Taster

=92/8

polymorphism

(source)

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

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1-111312237-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over