chr1-203220424-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003465.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	NM_003465.3	MANE Select	c.730-575A>G		intron	N/A	NP_003456.1
	CHIT1	NM_001256125.2		c.673-575A>G		intron	N/A	NP_001243054.2
	CHIT1	NR_045784.2		n.767-575A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.730-575A>G		intron	N/A	ENSP00000356198.1
	CHIT1	ENST00000491855.5	TSL:1	n.730-575A>G		intron	N/A	ENSP00000423778.1
	CHIT1	ENST00000503786.1	TSL:1	n.730-575A>G		intron	N/A	ENSP00000421617.1

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

African (AFR) AF: 0.528 AC: 21903 AN: 41464

American (AMR) AF: 0.630 AC: 9627 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1894 AN: 3468

East Asian (EAS) AF: 0.935 AC: 4839 AN: 5178

South Asian (SAS) AF: 0.711 AC: 3422 AN: 4816

European-Finnish (FIN) AF: 0.487 AC: 5145 AN: 10558

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33390 AN: 67948

Other (OTH) AF: 0.551 AC: 1163 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.82
PhyloP100		0.044
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1556854; hg19: chr1-203189552;