NM_201653.4:c.304G>A

Variant names:

• chr1-111314586-G-A
• rs3818822
• NM_201653.4:c.304G>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 38 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201653.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIA	NM_201653.4	MANE Select	c.304G>A	p.Gly102Arg	missense	Exon 5 of 12	NP_970615.2	Q9BZP6-1
	CHIA	NM_001258001.2		c.-21G>A		5_prime_UTR	Exon 4 of 11	NP_001244930.1	Q9BZP6-2
	CHIA	NM_001258003.2		c.-21G>A		5_prime_UTR	Exon 3 of 10	NP_001244932.1	Q9BZP6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIA	ENST00000369740.6	TSL:1 MANE Select	c.304G>A	p.Gly102Arg	missense	Exon 5 of 12	ENSP00000358755.1	Q9BZP6-1
	CHIA	ENST00000422815.5	TSL:1	c.136G>A	p.Gly46Arg	missense	Exon 2 of 9	ENSP00000387671.1	Q5VUV5
	CHIA	ENST00000430615.1	TSL:1	c.-21G>A		5_prime_UTR	Exon 3 of 10	ENSP00000391132.1	Q9BZP6-2

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

GnomAD2 exomes AF: 0.108 AC: 26949 AN: 249364 AF XY: 0.111

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 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

African (AFR) AF: 0.168 AC: 5613 AN: 33374

American (AMR) AF: 0.0530 AC: 2368 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0728 AC: 1902 AN: 26110

East Asian (EAS) AF: 0.0861 AC: 3418 AN: 39676

South Asian (SAS) AF: 0.158 AC: 13632 AN: 86144

European-Finnish (FIN) AF: 0.0819 AC: 4372 AN: 53404

Middle Eastern (MID) AF: 0.0886 AC: 510 AN: 5758

European-Non Finnish (NFE) AF: 0.111 AC: 123384 AN: 1109006

Other (OTH) AF: 0.105 AC: 6317 AN: 60270

GnomAD4 genome AF: 0.121 AC: 18464 AN: 152214 Hom.: 1193 Cov.: 32 AF XY: 0.121 AC XY: 9023 AN XY: 74428

African (AFR) AF: 0.171 AC: 7094 AN: 41500

American (AMR) AF: 0.0825 AC: 1262 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0758 AC: 263 AN: 3470

East Asian (EAS) AF: 0.0955 AC: 496 AN: 5192

South Asian (SAS) AF: 0.155 AC: 749 AN: 4820

European-Finnish (FIN) AF: 0.0697 AC: 739 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7564 AN: 68016

Other (OTH) AF: 0.108 AC: 228 AN: 2112

Alfa AF: 0.111 Hom.: 3654

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 v4.9

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
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		8.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.31		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
Mutation Taster		=207/93	polymorphism (auto)

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