chr1-111315329-A-G

Variant names:

• chr1-111315329-A-G
• rs61756687
• NM_201653.4:c.374A>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.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. 14/21 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 0.11 (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
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201653.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIA	NM_201653.4	MANE Select	c.374A>G	p.Lys125Arg	missense	Exon 6 of 12	NP_970615.2	Q9BZP6-1
	CHIA	NM_001258001.2		c.50A>G	p.Lys17Arg	missense	Exon 5 of 11	NP_001244930.1	Q9BZP6-2
	CHIA	NM_001258003.2		c.50A>G	p.Lys17Arg	missense	Exon 4 of 10	NP_001244932.1	Q9BZP6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIA	ENST00000369740.6	TSL:1 MANE Select	c.374A>G	p.Lys125Arg	missense	Exon 6 of 12	ENSP00000358755.1	Q9BZP6-1
	CHIA	ENST00000422815.5	TSL:1	c.206A>G	p.Lys69Arg	missense	Exon 3 of 9	ENSP00000387671.1	Q5VUV5
	CHIA	ENST00000430615.1	TSL:1	c.50A>G	p.Lys17Arg	missense	Exon 4 of 10	ENSP00000391132.1	Q9BZP6-2

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

GnomAD2 exomes AF: 0.108 AC: 27261 AN: 251414 AF XY: 0.112

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 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

African (AFR) AF: 0.0373 AC: 1248 AN: 33458

American (AMR) AF: 0.0561 AC: 2511 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0860 AC: 2247 AN: 26136

East Asian (EAS) AF: 0.00350 AC: 139 AN: 39696

South Asian (SAS) AF: 0.101 AC: 8736 AN: 86240

European-Finnish (FIN) AF: 0.152 AC: 8096 AN: 53420

Middle Eastern (MID) AF: 0.116 AC: 633 AN: 5468

European-Non Finnish (NFE) AF: 0.153 AC: 169732 AN: 1111636

Other (OTH) AF: 0.126 AC: 7595 AN: 60340

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

African (AFR) AF: 0.0411 AC: 1704 AN: 41446

American (AMR) AF: 0.0861 AC: 1314 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0887 AC: 308 AN: 3472

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5168

South Asian (SAS) AF: 0.0961 AC: 462 AN: 4806

European-Finnish (FIN) AF: 0.154 AC: 1622 AN: 10548

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.153 AC: 10369 AN: 67948

Other (OTH) AF: 0.113 AC: 238 AN: 2108

Alfa AF: 0.133 Hom.: 4938

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 v4.9

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
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.14
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.044
Sift	Benign	0.37	T
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.063
MPC		0.025
ClinPred		0.0043	T
GERP RS		-0.80
Varity_R		0.14
gMVP		0.39
Mutation Taster		=293/7	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: rs61756687; hg19: chr1-111857951;