rs2275253

Positions:

• chr1-111319219-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.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. 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 0.69 (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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIA	NM_201653.4	c.1015A>G	p.Ile339Val	missense_variant	10/12	ENST00000369740.6	NP_970615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6	c.1015A>G	p.Ile339Val	missense_variant	10/12	1	NM_201653.4	ENSP00000358755	P1
	ENST00000426321.1	n.149-1292T>C		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.640 AC: 160714 AN: 251244 Hom.: 54010 AF XY: 0.655 AC XY: 88938 AN XY: 135778

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 SAS exome AF: 0.758

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

Gnomad4 AFR exome AF: 0.785

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.704

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.755

Gnomad4 FIN exome AF: 0.639

Gnomad4 NFE exome AF: 0.706

Gnomad4 OTH exome AF: 0.685

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

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.653

Alfa AF: 0.698 Hom.: 95121

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 v4.3

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;.;T;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.31	T;.;.;T;T;.;T;T
MetaRNN	Benign	0.0000012	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.50	.;.;N;.;N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.42	N;N;N;N;N;N;N;N
REVEL	Benign	0.010
Sift	Benign	0.75	T;T;T;T;T;T;T;T
Sift4G	Benign	0.81	T;T;T;T;T;T;T;T
Polyphen		0.0	.;.;B;.;B;.;.;.
Vest4		0.030, 0.017, 0.018, 0.020
MPC		0.024
ClinPred		0.0033	T
GERP RS		-3.2
Varity_R		0.11
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs2275253; hg19: chr1-111861841; COSMIC: COSV58474372; COSMIC: COSV58474372;