1-203228129-T-G

Variant names:

• chr1-203228129-T-G
• rs2486072
• NM_003465.3:c.55+404A>C

Variant summary

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

The NM_003465.3(CHIT1):​c.55+404A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,074 control chromosomes in the GnomAD database, including 15,018 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 0.43 (15018 hom., cov: 33)
• Consequence: CHIT1 NM_003465.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 11 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 = 0.855 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.55+404A>C		intron	N/A	NP_003456.1	Q13231-1
	CHIT1	NM_001256125.2		c.55+404A>C		intron	N/A	NP_001243054.2	Q13231-4
	CHIT1	NR_045784.2		n.92+404A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.55+404A>C		intron	N/A	ENSP00000356198.1	Q13231-1
	CHIT1	ENST00000491855.5	TSL:1	n.55+404A>C		intron	N/A	ENSP00000423778.1	Q13231-2
	CHIT1	ENST00000503786.1	TSL:1	n.55+404A>C		intron	N/A	ENSP00000421617.1	D6REY1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65003 AN: 151956 Hom.: 15003 Cov.: 33

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.428 AC: 65058 AN: 152074 Hom.: 15018 Cov.: 33 AF XY: 0.436 AC XY: 32386 AN XY: 74344

African (AFR) AF: 0.471 AC: 19521 AN: 41460

American (AMR) AF: 0.511 AC: 7812 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3470

East Asian (EAS) AF: 0.876 AC: 4531 AN: 5172

South Asian (SAS) AF: 0.646 AC: 3118 AN: 4826

European-Finnish (FIN) AF: 0.292 AC: 3091 AN: 10584

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24189 AN: 67960

Other (OTH) AF: 0.428 AC: 905 AN: 2114

Alfa AF: 0.390 Hom.: 21757

Bravo AF: 0.443

Asia WGS AF: 0.721 AC: 2503 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	0.14
DANN	Benign	0.59
PhyloP100		-1.8
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: rs2486072; hg19: chr1-203197257;