1-203226749-G-T

Position:

• chr1-203226749-G-T

Variant summary

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

The ENST00000367229.6(CHIT1):​c.56-879C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 150,082 control chromosomes in the GnomAD database, including 2,998 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 0.20 (2998 hom., cov: 30)
• Consequence: CHIT1 ENST00000367229.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIT1	NM_003465.3	c.56-879C>A		intron_variant		ENST00000367229.6	NP_003456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000367229.6	c.56-879C>A		intron_variant		1	NM_003465.3	ENSP00000356198	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 29934 AN: 149964 Hom.: 2997 Cov.: 30

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.200 AC: 29945 AN: 150082 Hom.: 2998 Cov.: 30 AF XY: 0.198 AC XY: 14545 AN XY: 73394

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.183

Alfa AF: 0.184 Hom.: 3473

Bravo AF: 0.199

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.62

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: rs3766537; hg19: chr1-203195877;