rs186163063

Variant names:

• chr1-111312333-A-G
• rs186163063
• NM_201653.4:c.199A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-111312333-A-G
• chr1-111312333-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201653.4(CHIA):​c.199A>G​(p.Thr67Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T67S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CHIA NM_201653.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077950835).

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.199A>G	p.Thr67Ala	missense	Exon 4 of 12	NP_970615.2	Q9BZP6-1
	CHIA	NM_001258001.2		c.-68+615A>G		intron	N/A	NP_001244930.1	Q9BZP6-2
	CHIA	NM_001258003.2		c.-68+615A>G		intron	N/A	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.199A>G	p.Thr67Ala	missense	Exon 4 of 12	ENSP00000358755.1	Q9BZP6-1
	CHIA	ENST00000422815.5	TSL:1	c.90-2207A>G		intron	N/A	ENSP00000387671.1	Q5VUV5
	CHIA	ENST00000430615.1	TSL:1	c.-68+615A>G		intron	N/A	ENSP00000391132.1	Q9BZP6-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249480 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461868 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.34
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.74	N
PhyloP100		1.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.042
Sift	Benign	0.52	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.35		Loss of glycosylation at T67 (P = 0.0589)
MVP		0.22
MPC		0.027
ClinPred		0.039	T
GERP RS		3.8
Varity_R		0.22
gMVP		0.46
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs186163063; hg19: chr1-111854955;