NM_201653.4:c.56-124T>C

Variant names:

• chr1-111312066-T-C
• rs10494133
• NM_201653.4:c.56-124T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 (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 rank	MANE	Protein	UniProt
CHIA	NM_201653.4	c.56-124T>C		intron_variant	Intron 3 of 11	ENST00000369740.6	NP_970615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6	c.56-124T>C		intron_variant	Intron 3 of 11	1	NM_201653.4	ENSP00000358755.1

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

African (AFR) AF: 0.179 AC: 2929 AN: 16352

American (AMR) AF: 0.0801 AC: 2621 AN: 32702

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 2792 AN: 16782

East Asian (EAS) AF: 0.000231 AC: 8 AN: 34642

South Asian (SAS) AF: 0.0942 AC: 5505 AN: 58434

European-Finnish (FIN) AF: 0.0691 AC: 2964 AN: 42896

Middle Eastern (MID) AF: 0.134 AC: 311 AN: 2328

European-Non Finnish (NFE) AF: 0.116 AC: 40909 AN: 351792

Other (OTH) AF: 0.115 AC: 3570 AN: 30962

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

African (AFR) AF: 0.190 AC: 7877 AN: 41478

American (AMR) AF: 0.101 AC: 1541 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 643 AN: 3458

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.0918 AC: 443 AN: 4826

European-Finnish (FIN) AF: 0.0747 AC: 791 AN: 10584

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8219 AN: 67992

Other (OTH) AF: 0.133 AC: 280 AN: 2112

Alfa AF: 0.125 Hom.: 734

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
PhyloP100		-1.2
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: rs10494133; hg19: chr1-111854688;