1-111314575-G-C

Variant names:

• chr1-111314575-G-C
• rs1266342181
• NM_201653.4:c.293G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_201653.4(CHIA):​c.293G>C​(p.Gly98Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G98D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHIA NM_201653.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.80
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIA	NM_201653.4	c.293G>C	p.Gly98Ala	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.293G>C	p.Gly98Ala	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

Alfa AF: 0.000224 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	.;T;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;.;D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Uncertain	-0.074	T
MutationAssessor	Pathogenic	4.7	.;H;H
PhyloP100		6.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.9	D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.020	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.80
MutPred		0.94		.;Gain of catalytic residue at G98 (P = 0.1714);Gain of catalytic residue at G98 (P = 0.1714);
MVP		0.60
MPC		0.22
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.85
gMVP		0.94
Mutation Taster		=55/45	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

dbSNP: rs1266342181; hg19: chr1-111857197;