rs2275254

chr1-111319352-T-C

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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=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/exons	MANE	UniProt
CHIA	NM_201653.4	c.1061T>C	p.Phe354Ser	missense_variant	11/12	ENST00000369740.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIA	ENST00000369740.6	c.1061T>C	p.Phe354Ser	missense_variant	11/12	1	NM_201653.4	P1
	ENST00000426321.1	n.149-1425A>G		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.501 AC: 125924 AN: 251244 Hom.: 33553 AF XY: 0.520 AC XY: 70543 AN XY: 135786

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 SAS exome AF: 0.586

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

Gnomad4 AFR exome AF: 0.337

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.550

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.484

Alfa AF: 0.561 Hom.: 63106

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
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
MutationTaster	Benign	0.21	P;P;P;P;P;P
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

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: rs2275254; hg19: chr1-111861974; COSMIC: COSV58474000; COSMIC: COSV58474000;