1-203226749-G-T

Variant names:

• chr1-203226749-G-T
• rs3766537
• NM_003465.3:c.56-879C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003465.3(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 NM_003465.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	NM_003465.3	MANE Select	c.56-879C>A		intron	N/A	NP_003456.1	Q13231-1
	CHIT1	NM_001256125.2		c.56-879C>A		intron	N/A	NP_001243054.2	Q13231-4
	CHIT1	NR_045784.2		n.93-879C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.56-879C>A		intron	N/A	ENSP00000356198.1	Q13231-1
	CHIT1	ENST00000491855.5	TSL:1	n.56-879C>A		intron	N/A	ENSP00000423778.1	Q13231-2
	CHIT1	ENST00000503786.1	TSL:1	n.56-879C>A		intron	N/A	ENSP00000421617.1	D6REY1

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

African (AFR) AF: 0.224 AC: 9119 AN: 40764

American (AMR) AF: 0.179 AC: 2714 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 774 AN: 3442

East Asian (EAS) AF: 0.253 AC: 1275 AN: 5038

South Asian (SAS) AF: 0.191 AC: 896 AN: 4700

European-Finnish (FIN) AF: 0.161 AC: 1692 AN: 10500

Middle Eastern (MID) AF: 0.169 AC: 49 AN: 290

European-Non Finnish (NFE) AF: 0.193 AC: 12944 AN: 67216

Other (OTH) AF: 0.183 AC: 382 AN: 2088

Alfa AF: 0.191 Hom.: 9189

Bravo AF: 0.199

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.62
PhyloP100		-0.60
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: rs3766537; hg19: chr1-203195877;