1-111314584-T-G

Variant names:

• chr1-111314584-T-G
• ENST00000430615.1:c.-23T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000430615.1(CHIA):​c.-23T>G variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CHIA ENST00000430615.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIA	NM_201653.4	c.302T>G	p.Phe101Cys	missense_variant	Exon 5 of 12	ENST00000369740.6	NP_970615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6	c.302T>G	p.Phe101Cys	missense_variant	Exon 5 of 12	1	NM_201653.4	ENSP00000358755.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.302T>G (p.F101C) alteration is located in exon 5 (coding exon 4) of the CHIA gene. This alteration results from a T to G substitution at nucleotide position 302, causing the phenylalanine (F) at amino acid position 101 to be replaced by a cysteine (C). 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	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	.;T;T
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.6	.;H;H
PhyloP100		5.2
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.9	D;D;D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.67
MutPred		0.70		.;Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);
MVP		0.51
MPC		0.12
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.92
gMVP		0.77
Mutation Taster		=216/84	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

Other links and lift over

hg19: chr1-111857206;