rs61756687

Positions:

• chr1-111315329-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.374A>G​(p.Lys125Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,613,068 control chromosomes in the GnomAD database, including 16,038 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.11 (1086 hom., cov: 31)
  • Exomes 𝑓: 0.14 (14952 hom.)
• Consequence: CHIA NM_201653.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018067956).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHIA	NM_201653.4	c.374A>G	p.Lys125Arg	missense_variant	6/12	ENST00000369740.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIA	ENST00000369740.6	c.374A>G	p.Lys125Arg	missense_variant	6/12	1	NM_201653.4	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16223 AN: 151832 Hom.: 1087 Cov.: 31

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0887

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.108 AC: 27261 AN: 251414 Hom.: 1807 AF XY: 0.112 AC XY: 15239 AN XY: 135868

Gnomad AFR exome AF: 0.0376

Gnomad AMR exome AF: 0.0541

Gnomad ASJ exome AF: 0.0895

Gnomad EAS exome AF: 0.00837

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.138 AC: 200937 AN: 1461118 Hom.: 14952 Cov.: 31 AF XY: 0.138 AC XY: 99950 AN XY: 726898

Gnomad4 AFR exome AF: 0.0373

Gnomad4 AMR exome AF: 0.0561

Gnomad4 ASJ exome AF: 0.0860

Gnomad4 EAS exome AF: 0.00350

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.107 AC: 16223 AN: 151950 Hom.: 1086 Cov.: 31 AF XY: 0.105 AC XY: 7829 AN XY: 74270

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.0861

Gnomad4 ASJ AF: 0.0887

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.0961

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.113

Alfa AF: 0.136 Hom.: 2159

Bravo AF: 0.0966

TwinsUK AF: 0.149 AC: 554

ALSPAC AF: 0.152 AC: 585

ESP6500AA AF: 0.0454 AC: 200

ESP6500EA AF: 0.147 AC: 1262

ExAC AF: 0.110 AC: 13380

Asia WGS AF: 0.0630 AC: 221 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.44	T;.;T;T
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	0.76	P;P;P;P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.044
Sift	Benign	0.37	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.0020	.;B;B;.
Vest4		0.063, 0.064, 0.071
MPC		0.025
ClinPred		0.0043	T
GERP RS		-0.80
Varity_R		0.14
gMVP		0.39

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: rs61756687; hg19: chr1-111857951;