rs2256721

Variant names:

• chr1-111320330-T-G
• rs2256721
• NM_201653.4:c.1295T>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.1295T>G​(p.Val432Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,613,944 control chromosomes in the GnomAD database, including 389,913 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 (37018 hom., cov: 32)
  • Exomes 𝑓: 0.69 (352895 hom.)
• Consequence: CHIA NM_201653.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 33 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=9.624317E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIA	NM_201653.4	c.1295T>G	p.Val432Gly	missense_variant	Exon 12 of 12	ENST00000369740.6	NP_970615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6	c.1295T>G	p.Val432Gly	missense_variant	Exon 12 of 12	1	NM_201653.4	ENSP00000358755.1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105031 AN: 152014 Hom.: 36992 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.652

GnomAD2 exomes AF: 0.639 AC: 160500 AN: 251014 AF XY: 0.655

Gnomad AFR exome AF: 0.772

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.706

Gnomad EAS exome AF: 0.454

Gnomad FIN exome AF: 0.637

Gnomad NFE exome AF: 0.700

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.690 AC: 1009264 AN: 1461812 Hom.: 352895 Cov.: 71 AF XY: 0.694 AC XY: 504802 AN XY: 727204

African (AFR) AF: 0.781 AC: 26137 AN: 33480

American (AMR) AF: 0.366 AC: 16346 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 18388 AN: 26134

East Asian (EAS) AF: 0.458 AC: 18181 AN: 39696

South Asian (SAS) AF: 0.756 AC: 65196 AN: 86258

European-Finnish (FIN) AF: 0.639 AC: 34117 AN: 53416

Middle Eastern (MID) AF: 0.728 AC: 4198 AN: 5766

European-Non Finnish (NFE) AF: 0.706 AC: 785357 AN: 1111958

Other (OTH) AF: 0.685 AC: 41344 AN: 60392

GnomAD4 genome AF: 0.691 AC: 105106 AN: 152132 Hom.: 37018 Cov.: 32 AF XY: 0.686 AC XY: 50995 AN XY: 74362

African (AFR) AF: 0.775 AC: 32148 AN: 41502

American (AMR) AF: 0.493 AC: 7531 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2423 AN: 3468

East Asian (EAS) AF: 0.457 AC: 2357 AN: 5154

South Asian (SAS) AF: 0.742 AC: 3579 AN: 4824

European-Finnish (FIN) AF: 0.643 AC: 6806 AN: 10578

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47965 AN: 68014

Other (OTH) AF: 0.650 AC: 1373 AN: 2112

Alfa AF: 0.697 Hom.: 124765

Bravo AF: 0.673

TwinsUK AF: 0.702 AC: 2602

ALSPAC AF: 0.718 AC: 2769

ESP6500AA AF: 0.768 AC: 3382

ESP6500EA AF: 0.697 AC: 5991

ExAC AF: 0.655 AC: 79499

Asia WGS AF: 0.573 AC: 1996 AN: 3478

EpiCase AF: 0.715

EpiControl AF: 0.708

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.4
DANN	Benign	0.80
DEOGEN2	Benign	0.081	.;.;T;.;T;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.011	T;.;.;T;T;.;T;T
MetaRNN	Benign	9.6e-7	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-3.0	.;.;N;.;N;.;.;.
PhyloP100		2.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	4.7	N;N;N;N;N;N;N;N
REVEL	Benign	0.29
Sift	Benign	1.0	T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.0	.;.;B;.;B;.;.;.
Vest4		0.058, 0.041, 0.055, 0.036, 0.070, 0.039
MPC		0.030
ClinPred		0.0016	T
GERP RS		1.5
Varity_R		0.050
gMVP		0.66
Mutation Taster		=100/0	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: rs2256721; hg19: chr1-111862952; COSMIC: COSV58473784; COSMIC: COSV58473784;