rs2486070

Positions:

• chr1-203226561-G-A

Variant summary

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

The NM_003465.3(CHIT1):​c.56-691C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,134 control chromosomes in the GnomAD database, including 4,124 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 0.22 (4124 hom., cov: 31)
• Consequence: CHIT1 NM_003465.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHIT1	NM_003465.3	c.56-691C>T		intron_variant		ENST00000367229.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIT1	ENST00000367229.6	c.56-691C>T		intron_variant		1	NM_003465.3	P1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32912 AN: 152016 Hom.: 4113 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.217 AC: 32955 AN: 152134 Hom.: 4124 Cov.: 31 AF XY: 0.222 AC XY: 16477 AN XY: 74386

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.229

Alfa AF: 0.196 Hom.: 1494

Bravo AF: 0.224

Asia WGS AF: 0.447 AC: 1552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.76

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: rs2486070; hg19: chr1-203195689;