1-111310959-C-T

Variant names:

• chr1-111310959-C-T
• rs4240530
• NM_201653.4:c.25+467C>T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIA	NM_201653.4	c.25+467C>T		intron_variant	Intron 2 of 11	ENST00000369740.6	NP_970615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIA	ENST00000369740.6	c.25+467C>T		intron_variant	Intron 2 of 11	1	NM_201653.4	ENSP00000358755.1

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

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.719

Alfa AF: 0.695 Hom.: 19771

Bravo AF: 0.695

Asia WGS AF: 0.734 AC: 2545 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.26

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: rs4240530; hg19: chr1-111853581; COSMIC: COSV58474448;