rs2275253

Variant names:

• chr1-111319219-A-G
• rs2275253
• NM_201653.4:c.1015A>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.1015A>G​(p.Ile339Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,613,838 control chromosomes in the GnomAD database, including 390,150 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 0.69 (37183 hom., cov: 32)
  • Exomes 𝑓: 0.69 (352967 hom.)
• Consequence: CHIA NM_201653.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 35 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]

ENSG00000229283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1972289E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 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.1015A>G	p.Ile339Val	missense	Exon 10 of 12	NP_970615.2	Q9BZP6-1
	CHIA	NM_001258001.2		c.691A>G	p.Ile231Val	missense	Exon 9 of 11	NP_001244930.1	Q9BZP6-2
	CHIA	NM_001258003.2		c.691A>G	p.Ile231Val	missense	Exon 8 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.1015A>G	p.Ile339Val	missense	Exon 10 of 12	ENSP00000358755.1	Q9BZP6-1
	CHIA	ENST00000422815.5	TSL:1	c.847A>G	p.Ile283Val	missense	Exon 7 of 9	ENSP00000387671.1	Q5VUV5
	CHIA	ENST00000430615.1	TSL:1	c.691A>G	p.Ile231Val	missense	Exon 8 of 10	ENSP00000391132.1	Q9BZP6-2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105232 AN: 151988 Hom.: 37155 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.654

GnomAD2 exomes AF: 0.640 AC: 160714 AN: 251244 AF XY: 0.655

Gnomad AFR exome AF: 0.778

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.707

Gnomad EAS exome AF: 0.453

Gnomad FIN exome AF: 0.637

Gnomad NFE exome AF: 0.700

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.690 AC: 1009270 AN: 1461732 Hom.: 352967 Cov.: 70 AF XY: 0.694 AC XY: 504798 AN XY: 727176

African (AFR) AF: 0.785 AC: 26286 AN: 33480

American (AMR) AF: 0.367 AC: 16390 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 18407 AN: 26132

East Asian (EAS) AF: 0.454 AC: 18021 AN: 39698

South Asian (SAS) AF: 0.755 AC: 65145 AN: 86248

European-Finnish (FIN) AF: 0.639 AC: 34111 AN: 53414

Middle Eastern (MID) AF: 0.727 AC: 4195 AN: 5768

European-Non Finnish (NFE) AF: 0.706 AC: 785329 AN: 1111882

Other (OTH) AF: 0.685 AC: 41386 AN: 60394

GnomAD4 genome AF: 0.692 AC: 105308 AN: 152106 Hom.: 37183 Cov.: 32 AF XY: 0.687 AC XY: 51081 AN XY: 74370

African (AFR) AF: 0.780 AC: 32360 AN: 41506

American (AMR) AF: 0.494 AC: 7551 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2434 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2350 AN: 5168

South Asian (SAS) AF: 0.742 AC: 3580 AN: 4824

European-Finnish (FIN) AF: 0.643 AC: 6799 AN: 10570

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47933 AN: 67962

Other (OTH) AF: 0.653 AC: 1377 AN: 2110

Alfa AF: 0.696 Hom.: 185110

Bravo AF: 0.675

TwinsUK AF: 0.702 AC: 2604

ALSPAC AF: 0.719 AC: 2770

ESP6500AA AF: 0.773 AC: 3404

ESP6500EA AF: 0.697 AC: 5991

ExAC AF: 0.655 AC: 79549

Asia WGS AF: 0.572 AC: 1993 AN: 3478

EpiCase AF: 0.715

EpiControl AF: 0.707

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.038
DANN	Benign	0.70
DEOGEN2	Benign	0.079	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.50	N
PhyloP100		-0.44
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.010
Sift	Benign	0.75	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.030
MPC		0.024
ClinPred		0.0033	T
GERP RS		-3.2
Varity_R		0.11
gMVP		0.12
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2275253; hg19: chr1-111861841; COSMIC: COSV58474372; COSMIC: COSV58474372;