chr1-203215638-T-C

Position:

• chr1-203215638-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000479483.1(CHIT1):​n.283+2101A>G variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIT1	ENST00000479483.1	n.283+2101A>G		intron_variant, non_coding_transcript_variant		3
CHIT1	ENST00000484834.5	n.5388+2101A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.214

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs872583; hg19: chr1-203184766;