NM_201653.4:c.25+467C>T

Variant names:

• chr1-111310959-C-T
• rs4240530
• NM_201653.4:c.25+467C>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.25+467C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,048 control chromosomes in the GnomAD database, including 36,018 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 0.68 (36018 hom., cov: 32)
• Consequence: CHIA NM_201653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 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.25+467C>T		intron	N/A	NP_970615.2	Q9BZP6-1
	CHIA	NM_001258001.2		c.-98+467C>T		intron	N/A	NP_001244930.1	Q9BZP6-2
	CHIA	NM_001258003.2		c.-97-730C>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.25+467C>T		intron	N/A	ENSP00000358755.1	Q9BZP6-1
	CHIA	ENST00000422815.5	TSL:1	c.90-3581C>T		intron	N/A	ENSP00000387671.1	Q5VUV5
	CHIA	ENST00000430615.1	TSL:1	c.-98+467C>T		intron	N/A	ENSP00000391132.1	Q9BZP6-2

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103983 AN: 151930 Hom.: 35995 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.718

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.684 AC: 104065 AN: 152048 Hom.: 36018 Cov.: 32 AF XY: 0.684 AC XY: 50863 AN XY: 74350

African (AFR) AF: 0.582 AC: 24122 AN: 41428

American (AMR) AF: 0.794 AC: 12127 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2404 AN: 3464

East Asian (EAS) AF: 0.846 AC: 4387 AN: 5188

South Asian (SAS) AF: 0.621 AC: 2993 AN: 4816

European-Finnish (FIN) AF: 0.695 AC: 7349 AN: 10576

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48216 AN: 67986

Other (OTH) AF: 0.719 AC: 1520 AN: 2114

Alfa AF: 0.695 Hom.: 21640

Bravo AF: 0.695

Asia WGS AF: 0.734 AC: 2545 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.26
PhyloP100		-1.1
PromoterAI		0.0026	Neutral
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: rs4240530; hg19: chr1-111853581; COSMIC: COSV58474448;