rs143439055

Variant names:

• chr1-203217736-TACTC-T
• rs143439055
• NM_003465.3:c.1155_1156+2delGAGT

Your query was ambiguous. Multiple possible variants found:

• chr1-203217736-TACTC-T
• chr1-203217736-TACTC-TACTCACTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003465.3(CHIT1):​c.1155_1156+2delGAGT​(p.Leu387fs) variant causes a frameshift, splice donor, splice region, intron change. The variant allele was found at a frequency of 0.0045 in 1,613,672 control chromosomes in the GnomAD database, including 264 homozygotes. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L385L) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.024 (129 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (135 hom.)
• Consequence: CHIT1 NM_003465.3 frameshift, splice_donor, splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 3.60
• 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 -10 ACMG points.

• BP6: Variant 1-203217736-TACTC-T is Benign according to our data. Variant chr1-203217736-TACTC-T is described in ClinVar as Benign. ClinVar VariationId is 294917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0796 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.1155_1156+2delGAGT	p.Leu387fs	frameshift splice_donor splice_region intron	Exon 10 of 11	NP_003456.1	Q13231-1
	CHIT1	NM_001256125.2		c.1098_1099+2delGAGT	p.Leu368fs	frameshift splice_donor splice_region intron	Exon 9 of 10	NP_001243054.2	Q13231-4
	CHIT1	NR_045784.2		n.1349_1350+2delGAGT		splice_donor splice_region intron non_coding_transcript_exon	Exon 11 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.1155_1156+2delGAGT	p.Leu387fs	frameshift splice_donor splice_region intron	Exon 10 of 11	ENSP00000356198.1	Q13231-1
	CHIT1	ENST00000503786.1	TSL:1	n.*226_*227+2delGAGT		splice_region non_coding_transcript_exon	Exon 11 of 13	ENSP00000421617.1	D6REY1
	CHIT1	ENST00000491855.5	TSL:1	n.1155_1156+2delGAGT		splice_donor splice_region intron non_coding_transcript_exon	Exon 10 of 12	ENSP00000423778.1	Q13231-2

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3586 AN: 151944 Hom.: 128 Cov.: 33

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00891

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00615 AC: 1545 AN: 251072 AF XY: 0.00436

Gnomad AFR exome AF: 0.0833

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00250 AC: 3648 AN: 1461610 Hom.: 135 AF XY: 0.00222 AC XY: 1616 AN XY: 727122

African (AFR) AF: 0.0854 AC: 2859 AN: 33470

American (AMR) AF: 0.00485 AC: 217 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5762

European-Non Finnish (NFE) AF: 0.000140 AC: 156 AN: 1111796

Other (OTH) AF: 0.00570 AC: 344 AN: 60374

GnomAD4 genome AF: 0.0237 AC: 3606 AN: 152062 Hom.: 129 Cov.: 33 AF XY: 0.0222 AC XY: 1652 AN XY: 74320

African (AFR) AF: 0.0819 AC: 3402 AN: 41518

American (AMR) AF: 0.00890 AC: 136 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 67954

Other (OTH) AF: 0.0166 AC: 35 AN: 2108

Alfa AF: 0.00336 Hom.: 12

Bravo AF: 0.0273

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Chitotriosidase deficiency (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6
Mutation Taster		=134/66	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		1.0		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.68		Position offset: -1
DS_DL_spliceai		1.0		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143439055; hg19: chr1-203186864; COSMIC: COSV106387709; COSMIC: COSV106387709;