rs10494133

Positions:

• chr1-111312066-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.56-124T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 739,016 control chromosomes in the GnomAD database, including 5,327 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.

• Frequency:
  • Genomes: 𝑓 0.13 (1544 hom., cov: 31)
  • Exomes 𝑓: 0.10 (3783 hom.)
• Consequence: CHIA NM_201653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIA	NM_201653.4	c.56-124T>C		intron_variant		ENST00000369740.6	NP_970615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6	c.56-124T>C		intron_variant		1	NM_201653.4	ENSP00000358755	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20051 AN: 152008 Hom.: 1547 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.105 AC: 61609 AN: 586890 Hom.: 3783 AF XY: 0.106 AC XY: 32945 AN XY: 312048

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.0801

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.000231

Gnomad4 SAS exome AF: 0.0942

Gnomad4 FIN exome AF: 0.0691

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.132 AC: 20061 AN: 152126 Hom.: 1544 Cov.: 31 AF XY: 0.127 AC XY: 9471 AN XY: 74394

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.0747

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.133

Alfa AF: 0.124 Hom.: 640

Bravo AF: 0.138

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.54

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: rs10494133; hg19: chr1-111854688;