Variant rs2275254 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_201653.4(CHIA):c.1061T>C(p.Phe354Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,613,680 control chromosomes in the GnomAD database, including 251,985 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 0.49 ( 19047 hom., cov: 32)

Exomes 𝑓: 0.56 ( 232938 hom. )

Consequence

CHIA
NM_201653.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.76

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.210208E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 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.1061T>C	p.Phe354Ser	missense_variant	11/12	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.1061T>C	p.Phe354Ser	missense_variant	11/12	1	NM_201653.4	ENSP00000358755.1		Q9BZP6-1

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73894

AN:

151916

Hom.:

19051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.580

Gnomad OTH

AF:

0.485

GnomAD3 exomes

AF:

0.501

AC:

125924

AN:

251244

Hom.:

33553

AF XY:

0.520

AC XY:

70543

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.336

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.622

Gnomad EAS exome

AF:

0.347

Gnomad SAS exome

AF:

0.586

Gnomad FIN exome

AF:

0.540

Gnomad NFE exome

AF:

0.575

Gnomad OTH exome

AF:

0.529

GnomAD4 exome

AF:

0.559

AC:

817720

AN:

1461646

Hom.:

232938

Cov.:

AF XY:

0.563

AC XY:

409108

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.337

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.617

Gnomad4 EAS exome

AF:

0.360

Gnomad4 SAS exome

AF:

0.584

Gnomad4 FIN exome

AF:

0.536

Gnomad4 NFE exome

AF:

0.582

Gnomad4 OTH exome

AF:

0.550

GnomAD4 genome

AF:

0.486

AC:

73899

AN:

152034

Hom.:

19047

Cov.:

AF XY:

0.482

AC XY:

35837

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.378

Gnomad4 ASJ

AF:

0.611

Gnomad4 EAS

AF:

0.352

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.551

Gnomad4 NFE

AF:

0.580

Gnomad4 OTH

AF:

0.484

Alfa

AF:

0.561

Hom.:

63106

Bravo

AF:

0.462

TwinsUK

AF:

0.586

AC:

2173

ALSPAC

AF:

0.581

AC:

2240

ESP6500AA

AF:

0.350

AC:

1541

ESP6500EA

AF:

0.576

AC:

4956

ExAC

AF:

0.508

AC:

61654

Asia WGS

AF:

0.432

AC:

1502

AN:

3478

EpiCase

AF:

0.598

EpiControl

AF:

0.588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

.;.;T;.;T;.;.;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.57

T;.;.;T;T;.;T;T

MetaRNN

Benign

0.00062

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

.;.;M;.;M;.;.;.

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.6

D;D;D;D;D;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.023

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D;D;D

Polyphen

1.0

.;.;D;.;D;.;.;.

Vest4

0.39, 0.31, 0.35

MPC

0.25

ClinPred

0.025

GERP RS

3.8

Varity_R

0.95

gMVP

0.83

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