chr1-203220424-T-C

Variant names:

• chr1-203220424-T-C
• rs1556854
• NM_003465.3:c.730-575A>G

Variant summary

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

The NM_003465.3(CHIT1):​c.730-575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,034 control chromosomes in the GnomAD database, including 22,731 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 0.54 (22731 hom., cov: 32)
• Consequence: CHIT1 NM_003465.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIT1	NM_003465.3	c.730-575A>G		intron_variant	Intron 7 of 10	ENST00000367229.6	NP_003456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000367229.6	c.730-575A>G		intron_variant	Intron 7 of 10	1	NM_003465.3	ENSP00000356198.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81729 AN: 151916 Hom.: 22697 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.538 AC: 81822 AN: 152034 Hom.: 22731 Cov.: 32 AF XY: 0.546 AC XY: 40595 AN XY: 74306

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.935

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.551

Alfa AF: 0.522 Hom.: 2598

Bravo AF: 0.545

Asia WGS AF: 0.810 AC: 2811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.82

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: rs1556854; hg19: chr1-203189552;