chr1-111312133-A-C

Variant names:

• chr1-111312133-A-C
• rs4423003
• NM_201653.4:c.56-57A>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.56-57A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,436,970 control chromosomes in the GnomAD database, including 707,229 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 0.96 (70494 hom., cov: 31)
  • Exomes 𝑓: 1.0 (636735 hom.)
• Consequence: CHIA NM_201653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIA	NM_201653.4	c.56-57A>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.56-57A>C		intron_variant	Intron 3 of 11	1	NM_201653.4	ENSP00000358755.1

Frequencies

GnomAD3 genomes AF: 0.961 AC: 146128 AN: 152126 Hom.: 70462 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.986

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.974

GnomAD4 exome AF: 0.995 AC: 1278767 AN: 1284726 Hom.: 636735 AF XY: 0.996 AC XY: 644772 AN XY: 647394

African (AFR) AF: 0.856 AC: 25505 AN: 29796

American (AMR) AF: 0.991 AC: 43988 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 24800 AN: 24934

East Asian (EAS) AF: 0.999 AC: 38762 AN: 38786

South Asian (SAS) AF: 1.00 AC: 82450 AN: 82474

European-Finnish (FIN) AF: 1.00 AC: 53039 AN: 53040

Middle Eastern (MID) AF: 0.987 AC: 4416 AN: 4474

European-Non Finnish (NFE) AF: 1.00 AC: 951997 AN: 952458

Other (OTH) AF: 0.990 AC: 53810 AN: 54378

GnomAD4 genome AF: 0.960 AC: 146211 AN: 152244 Hom.: 70494 Cov.: 31 AF XY: 0.962 AC XY: 71629 AN XY: 74460

African (AFR) AF: 0.864 AC: 35847 AN: 41510

American (AMR) AF: 0.986 AC: 15084 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3451 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5184 AN: 5188

South Asian (SAS) AF: 0.999 AC: 4814 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67967 AN: 68026

Other (OTH) AF: 0.974 AC: 2059 AN: 2114

Alfa AF: 0.979 Hom.: 3833

Bravo AF: 0.955

Asia WGS AF: 0.989 AC: 3440 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	0.55
DANN	Benign	0.54
PhyloP100		-1.1
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: rs4423003; hg19: chr1-111854755;