rs9943208
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBA1
The ENST00000367229.6(CHIT1):c.1060G>A(p.Gly354Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00451 in 1,613,924 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 133 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 135 hom. )
Consequence
CHIT1
ENST00000367229.6 missense
ENST00000367229.6 missense
Scores
10
5
3
Clinical Significance
Conservation
PhyloP100: 7.10
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP3
Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.008951932).
BP6
Variant 1-203217835-C-T is Benign according to our data. Variant chr1-203217835-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 472285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-203217835-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0796 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHIT1 | NM_003465.3 | c.1060G>A | p.Gly354Arg | missense_variant | 10/11 | ENST00000367229.6 | NP_003456.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHIT1 | ENST00000367229.6 | c.1060G>A | p.Gly354Arg | missense_variant | 10/11 | 1 | NM_003465.3 | ENSP00000356198 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0236 AC: 3591AN: 152206Hom.: 132 Cov.: 33
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GnomAD3 exomes AF: 0.00619 AC: 1547AN: 250120Hom.: 57 AF XY: 0.00437 AC XY: 591AN XY: 135140
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GnomAD4 exome AF: 0.00251 AC: 3663AN: 1461600Hom.: 135 Cov.: 34 AF XY: 0.00224 AC XY: 1630AN XY: 727084
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GnomAD4 genome AF: 0.0237 AC: 3611AN: 152324Hom.: 133 Cov.: 33 AF XY: 0.0222 AC XY: 1657AN XY: 74492
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Dec 16, 2015 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Chitotriosidase deficiency Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 18, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0162);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at