1-111312267-A-G

Variant names:

• chr1-111312267-A-G
• rs41282492
• NM_201653.4:c.133A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201653.4(CHIA):​c.133A>G​(p.Asn45Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,612,840 control chromosomes in the GnomAD database, including 12,455 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1586 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10869 hom.)
• Consequence: CHIA NM_201653.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012527168).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIA	NM_201653.4	MANE Select	c.133A>G	p.Asn45Asp	missense	Exon 4 of 12	NP_970615.2
	CHIA	NM_001258001.2		c.-68+549A>G		intron	N/A	NP_001244930.1
	CHIA	NM_001258003.2		c.-68+549A>G		intron	N/A	NP_001244932.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIA	ENST00000369740.6	TSL:1 MANE Select	c.133A>G	p.Asn45Asp	missense	Exon 4 of 12	ENSP00000358755.1
	CHIA	ENST00000422815.5	TSL:1	c.90-2273A>G		intron	N/A	ENSP00000387671.1
	CHIA	ENST00000430615.1	TSL:1	c.-68+549A>G		intron	N/A	ENSP00000391132.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20282 AN: 151996 Hom.: 1589 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.135

GnomAD2 exomes AF: 0.105 AC: 26253 AN: 249458 AF XY: 0.107

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.0838

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.0712

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.118 AC: 171794 AN: 1460726 Hom.: 10869 Cov.: 33 AF XY: 0.118 AC XY: 85669 AN XY: 726748

African (AFR) AF: 0.199 AC: 6664 AN: 33440

American (AMR) AF: 0.0879 AC: 3931 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4731 AN: 26128

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.0976 AC: 8416 AN: 86244

European-Finnish (FIN) AF: 0.0716 AC: 3823 AN: 53418

Middle Eastern (MID) AF: 0.133 AC: 766 AN: 5768

European-Non Finnish (NFE) AF: 0.123 AC: 136166 AN: 1110958

Other (OTH) AF: 0.121 AC: 7285 AN: 60348

GnomAD4 genome AF: 0.133 AC: 20291 AN: 152114 Hom.: 1586 Cov.: 31 AF XY: 0.129 AC XY: 9568 AN XY: 74366

African (AFR) AF: 0.196 AC: 8117 AN: 41470

American (AMR) AF: 0.101 AC: 1539 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3460

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.0918 AC: 442 AN: 4814

European-Finnish (FIN) AF: 0.0746 AC: 790 AN: 10594

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8211 AN: 67994

Other (OTH) AF: 0.134 AC: 282 AN: 2108

Alfa AF: 0.124 Hom.: 2505

Bravo AF: 0.140

TwinsUK AF: 0.121 AC: 449

ALSPAC AF: 0.124 AC: 476

ESP6500AA AF: 0.186 AC: 775

ESP6500EA AF: 0.116 AC: 976

ExAC AF: 0.107 AC: 12926

Asia WGS AF: 0.0510 AC: 176 AN: 3478

EpiCase AF: 0.125

EpiControl AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.062
DANN	Benign	0.35
DEOGEN2	Benign	0.091	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.23	N
PhyloP100		0.20
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.048
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.080
MPC		0.029
ClinPred		0.00062	T
GERP RS		-2.9
Varity_R		0.041
gMVP		0.63
Mutation Taster		=94/6	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: rs41282492; hg19: chr1-111854889; COSMIC: COSV107430108;