1-111312267-A-G

Position:

• chr1-111312267-A-G

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict 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 0.13 (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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHIA	NM_201653.4	c.133A>G	p.Asn45Asp	missense_variant	4/12	ENST00000369740.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIA	ENST00000369740.6	c.133A>G	p.Asn45Asp	missense_variant	4/12	1	NM_201653.4	P1

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

GnomAD3 exomes AF: 0.105 AC: 26253 AN: 249458 Hom.: 1607 AF XY: 0.107 AC XY: 14515 AN XY: 135340

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 SAS exome AF: 0.0944

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

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.0879

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0976

Gnomad4 FIN exome AF: 0.0716

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.121

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

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.0746

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.134

Alfa AF: 0.125 Hom.: 1865

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 v4.3

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;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;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.23	N;N
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.23	N;N
REVEL	Benign	0.048
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.080
MPC		0.029
ClinPred		0.00062	T
GERP RS		-2.9
Varity_R		0.041
gMVP		0.63

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: rs41282492; hg19: chr1-111854889;