1-111317290-G-T

Variant names:

• chr1-111317290-G-T
• rs10494134
• NM_201653.4:c.481-391G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201653.4(CHIA):​c.481-391G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 180,872 control chromosomes in the GnomAD database, including 13,603 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 0.36 (11120 hom., cov: 31)
  • Exomes 𝑓: 0.39 (2483 hom.)
• Consequence: CHIA NM_201653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 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.481-391G>T		intron	N/A	NP_970615.2	Q9BZP6-1
	CHIA	NM_001258001.2		c.157-391G>T		intron	N/A	NP_001244930.1	Q9BZP6-2
	CHIA	NM_001258003.2		c.157-391G>T		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.481-391G>T		intron	N/A	ENSP00000358755.1	Q9BZP6-1
	CHIA	ENST00000422815.5	TSL:1	c.313-391G>T		intron	N/A	ENSP00000387671.1	Q5VUV5
	CHIA	ENST00000430615.1	TSL:1	c.157-391G>T		intron	N/A	ENSP00000391132.1	Q9BZP6-2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54664 AN: 151826 Hom.: 11124 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.387 AC: 11205 AN: 28928 Hom.: 2483 Cov.: 0 AF XY: 0.387 AC XY: 5878 AN XY: 15206

African (AFR) AF: 0.139 AC: 161 AN: 1158

American (AMR) AF: 0.245 AC: 845 AN: 3454

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 261 AN: 638

East Asian (EAS) AF: 0.328 AC: 882 AN: 2688

South Asian (SAS) AF: 0.459 AC: 1553 AN: 3380

European-Finnish (FIN) AF: 0.433 AC: 331 AN: 764

Middle Eastern (MID) AF: 0.462 AC: 36 AN: 78

European-Non Finnish (NFE) AF: 0.429 AC: 6651 AN: 15516

Other (OTH) AF: 0.387 AC: 485 AN: 1252

GnomAD4 genome AF: 0.360 AC: 54658 AN: 151944 Hom.: 11120 Cov.: 31 AF XY: 0.360 AC XY: 26747 AN XY: 74258

African (AFR) AF: 0.175 AC: 7235 AN: 41442

American (AMR) AF: 0.279 AC: 4264 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1471 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1812 AN: 5160

South Asian (SAS) AF: 0.478 AC: 2300 AN: 4812

European-Finnish (FIN) AF: 0.476 AC: 5015 AN: 10540

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31230 AN: 67944

Other (OTH) AF: 0.358 AC: 755 AN: 2108

Alfa AF: 0.425 Hom.: 24025

Bravo AF: 0.330

Asia WGS AF: 0.382 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.66
PhyloP100		-0.045
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: rs10494134; hg19: chr1-111859912;