Variant rs3818822 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP4_StrongBA1

The NM_201653.4(CHIA):c.304G>A(p.Gly102Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,610,662 control chromosomes in the GnomAD database, including 10,911 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1193 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9718 hom. )

Consequence

CHIA
NM_201653.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.62

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:

CHIA (HGNC:):

CHIA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, BayesDel_noAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0019410551).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIA	NM_201653.4 linkuse as main transcript	c.304G>A	p.Gly102Arg	missense_variant	5/12	ENST00000369740.6	NP_970615.2	Q9BZP6-1A8K3T7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6 linkuse as main transcript	c.304G>A	p.Gly102Arg	missense_variant	5/12	1	NM_201653.4	ENSP00000358755.1		Q9BZP6-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18462

AN:

152096

Hom.:

1197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0828

Gnomad ASJ

AF:

0.0758

Gnomad EAS

AF:

0.0953

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0697

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.108

AC:

26949

AN:

249364

Hom.:

1670

AF XY:

0.111

AC XY:

15007

AN XY:

135286

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.0505

Gnomad ASJ exome

AF:

0.0704

Gnomad EAS exome

AF:

0.0994

Gnomad SAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.0775

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.111

AC:

161516

AN:

1458448

Hom.:

9718

Cov.:

AF XY:

0.112

AC XY:

81595

AN XY:

725738

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0530

Gnomad4 ASJ exome

AF:

0.0728

Gnomad4 EAS exome

AF:

0.0861

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.0819

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.121

AC:

18464

AN:

152214

Hom.:

1193

Cov.:

AF XY:

0.121

AC XY:

9023

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.0825

Gnomad4 ASJ

AF:

0.0758

Gnomad4 EAS

AF:

0.0955

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.0697

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.107

Hom.:

2320

Bravo

AF:

0.120

TwinsUK

AF:

0.107

AC:

398

ALSPAC

AF:

0.126

AC:

484

ESP6500AA

AF:

0.163

AC:

610

ESP6500EA

AF:

0.107

AC:

880

ExAC

AF:

0.113

AC:

13636

Asia WGS

AF:

0.116

AC:

408

AN:

3478

EpiCase

AF:

0.106

EpiControl

AF:

0.108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

.;T;T

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;.;D

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.6

.;H;H

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.9

D;D;D

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.30, 0.30

MutPred

0.31

.;Gain of MoRF binding (P = 0.054);Gain of MoRF binding (P = 0.054);

MPC

0.23

ClinPred

0.084

GERP RS

4.6

Varity_R

0.89

gMVP

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over