1-203215638-T-C

Variant names:

• chr1-203215638-T-C
• rs872583
• ENST00000479483.1:n.283+2101A>G

Variant summary

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

The ENST00000479483.1(CHIT1):​n.283+2101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,162 control chromosomes in the GnomAD database, including 3,617 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 0.19 (3617 hom., cov: 32)
• Consequence: CHIT1 ENST00000479483.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 9 publications found

Genes affected

CHIT1 (HGNC:1936): (chitinase 1) Chitotriosidase is secreted by activated human macrophages and is markedly elevated in plasma of Gaucher disease patients. The expression of chitotriosidase occurs only at a late stage of differentiation of monocytes to activated macrophages in culture. Human macrophages can synthesize a functional chitotriosidase, a highly conserved enzyme with a strongly regulated expression. This enzyme may play a role in the degradation of chitin-containing pathogens. Several alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000479483.1	n.283+2101A>G		intron_variant	Intron 1 of 1	3
CHIT1	ENST00000484834.5	n.5388+2101A>G		intron_variant	Intron 11 of 11	2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28650 AN: 152044 Hom.: 3606 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.188 AC: 28678 AN: 152162 Hom.: 3617 Cov.: 32 AF XY: 0.197 AC XY: 14618 AN XY: 74386

African (AFR) AF: 0.0656 AC: 2724 AN: 41522

American (AMR) AF: 0.264 AC: 4028 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2977 AN: 5162

South Asian (SAS) AF: 0.443 AC: 2135 AN: 4820

European-Finnish (FIN) AF: 0.180 AC: 1912 AN: 10600

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13483 AN: 67984

Other (OTH) AF: 0.214 AC: 453 AN: 2116

Alfa AF: 0.162 Hom.: 335

Bravo AF: 0.184

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.77
PhyloP100		-0.063

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs872583; hg19: chr1-203184766;