1-203220780-C-G

Variant names:

• chr1-203220780-C-G
• rs946257
• NM_003465.3:c.730-931G>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.730-931G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,094 control chromosomes in the GnomAD database, including 7,357 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 0.31 (7357 hom., cov: 32)
• Consequence: CHIT1 NM_003465.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 2 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 (AMR) allele frequency at 95% confidence interval = 0.351 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.730-931G>C		intron	N/A	NP_003456.1	Q13231-1
	CHIT1	NM_001256125.2		c.673-931G>C		intron	N/A	NP_001243054.2	Q13231-4
	CHIT1	NR_045784.2		n.767-931G>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.730-931G>C		intron	N/A	ENSP00000356198.1	Q13231-1
	CHIT1	ENST00000491855.5	TSL:1	n.730-931G>C		intron	N/A	ENSP00000423778.1	Q13231-2
	CHIT1	ENST00000503786.1	TSL:1	n.730-931G>C		intron	N/A	ENSP00000421617.1	D6REY1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46956 AN: 151976 Hom.: 7347 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.309 AC: 47000 AN: 152094 Hom.: 7357 Cov.: 32 AF XY: 0.312 AC XY: 23193 AN XY: 74338

African (AFR) AF: 0.271 AC: 11220 AN: 41476

American (AMR) AF: 0.359 AC: 5481 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1163 AN: 3464

East Asian (EAS) AF: 0.338 AC: 1751 AN: 5174

South Asian (SAS) AF: 0.263 AC: 1266 AN: 4822

European-Finnish (FIN) AF: 0.368 AC: 3893 AN: 10566

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21303 AN: 67988

Other (OTH) AF: 0.314 AC: 664 AN: 2116

Alfa AF: 0.228 Hom.: 570

Bravo AF: 0.308

Asia WGS AF: 0.335 AC: 1163 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	0.54
DANN	Benign	0.63
PhyloP100		-0.67
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: rs946257; hg19: chr1-203189908;