rs2275254

Variant names:

• chr1-111319352-T-C
• rs2275254
• NM_201653.4:c.1061T>C

Variant summary

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

The NM_201653.4(CHIA):​c.1061T>C​(p.Phe354Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,613,680 control chromosomes in the GnomAD database, including 251,985 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 0.49 (19047 hom., cov: 32)
  • Exomes 𝑓: 0.56 (232938 hom.)
• Consequence: CHIA NM_201653.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• Publications: 39 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=6.210208E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIA	NM_201653.4	c.1061T>C	p.Phe354Ser	missense_variant	Exon 11 of 12	ENST00000369740.6	NP_970615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6	c.1061T>C	p.Phe354Ser	missense_variant	Exon 11 of 12	1	NM_201653.4	ENSP00000358755.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73894 AN: 151916 Hom.: 19051 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.485

GnomAD2 exomes AF: 0.501 AC: 125924 AN: 251244 AF XY: 0.520

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.622

Gnomad EAS exome AF: 0.347

Gnomad FIN exome AF: 0.540

Gnomad NFE exome AF: 0.575

Gnomad OTH exome AF: 0.529

GnomAD4 exome AF: 0.559 AC: 817720 AN: 1461646 Hom.: 232938 Cov.: 54 AF XY: 0.563 AC XY: 409108 AN XY: 727140

African (AFR) AF: 0.337 AC: 11279 AN: 33476

American (AMR) AF: 0.293 AC: 13116 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 16128 AN: 26134

East Asian (EAS) AF: 0.360 AC: 14298 AN: 39700

South Asian (SAS) AF: 0.584 AC: 50406 AN: 86252

European-Finnish (FIN) AF: 0.536 AC: 28651 AN: 53416

Middle Eastern (MID) AF: 0.611 AC: 3521 AN: 5766

European-Non Finnish (NFE) AF: 0.582 AC: 647096 AN: 1111798

Other (OTH) AF: 0.550 AC: 33225 AN: 60386

GnomAD4 genome AF: 0.486 AC: 73899 AN: 152034 Hom.: 19047 Cov.: 32 AF XY: 0.482 AC XY: 35837 AN XY: 74318

African (AFR) AF: 0.345 AC: 14312 AN: 41456

American (AMR) AF: 0.378 AC: 5780 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2120 AN: 3470

East Asian (EAS) AF: 0.352 AC: 1818 AN: 5164

South Asian (SAS) AF: 0.570 AC: 2747 AN: 4818

European-Finnish (FIN) AF: 0.551 AC: 5821 AN: 10574

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39442 AN: 67964

Other (OTH) AF: 0.484 AC: 1021 AN: 2110

Alfa AF: 0.549 Hom.: 116116

Bravo AF: 0.462

TwinsUK AF: 0.586 AC: 2173

ALSPAC AF: 0.581 AC: 2240

ESP6500AA AF: 0.350 AC: 1541

ESP6500EA AF: 0.576 AC: 4956

ExAC AF: 0.508 AC: 61654

Asia WGS AF: 0.432 AC: 1502 AN: 3478

EpiCase AF: 0.598

EpiControl AF: 0.588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;.;T;.;T;.;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.57	T;.;.;T;T;.;T;T
MetaRNN	Benign	0.00062	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	.;.;M;.;M;.;.;.
PhyloP100		2.8
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.6	D;D;D;D;D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.023	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D;D
Polyphen		1.0	.;.;D;.;D;.;.;.
Vest4		0.39, 0.31, 0.35
MPC		0.25
ClinPred		0.025	T
GERP RS		3.8
Varity_R		0.95
gMVP		0.83
Mutation Taster		=97/3	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: rs2275254; hg19: chr1-111861974; COSMIC: COSV58474000; COSMIC: COSV58474000;