rs3818822

chr1-111314586-G-Achr1-111314586-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3 BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.62

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

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	UniProt
CHIA	NM_201653.4	c.304G>A	p.Gly102Arg	missense_variant	5/12	ENST00000369740.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIA	ENST00000369740.6	c.304G>A	p.Gly102Arg	missense_variant	5/12	1	NM_201653.4	P1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18462 AN: 152096 Hom.: 1197 Cov.: 32

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

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.: 30 AF XY: 0.112 AC XY: 81595 AN XY: 725738

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.: 32 AF XY: 0.121 AC XY: 9023 AN XY: 74428

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	T
BayesDel_noAF	Benign	-0.28
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.;D
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	0.0000034	P;P;P;P;P;P
PrimateAI	Uncertain	0.53	T
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	T
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

Other links and lift over

dbSNP: rs3818822; hg19: chr1-111857208; COSMIC: COSV58474676; COSMIC: COSV58474676;