chr1-203238392-T-C

Variant names:

• chr1-203238392-T-C
• rs2494287
• ENST00000484834.5:n.4382+2071A>G

Variant summary

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

The ENST00000484834.5(CHIT1):​n.4382+2071A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,170 control chromosomes in the GnomAD database, including 60,258 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 0.89 (60258 hom., cov: 31)
• Consequence: CHIT1 ENST00000484834.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 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	ENST00000484834.5	n.4382+2071A>G		intron_variant	Intron 3 of 11	2
CHIT1	ENST00000513472.5	n.151+2071A>G		intron_variant	Intron 3 of 7	3

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134932 AN: 152052 Hom.: 60216 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.887 AC: 135026 AN: 152170 Hom.: 60258 Cov.: 31 AF XY: 0.885 AC XY: 65866 AN XY: 74384

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.946

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.894

Alfa AF: 0.882 Hom.: 131035

Bravo AF: 0.873

Asia WGS AF: 0.801 AC: 2787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2494287; hg19: chr1-203207520;