rs2297950

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003465.3(CHIT1):c.304G>A(p.Gly102Ser) variant causes a missense change. The variant allele was found at a frequency of 0.301 in 1,611,948 control chromosomes in the GnomAD database, including 73,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6729 hom., cov: 30)

Exomes 𝑓: 0.30 ( 67051 hom. )

Consequence

CHIT1
NM_003465.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4O:2

Conservation

PhyloP100: 6.67

Publications

68 publications found

Variant links:

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]

CHIT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018247366).

BP6

Variant 1-203225058-C-T is Benign according to our data. Variant chr1-203225058-C-T is described in ClinVar as Benign. ClinVar VariationId is 9526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CHIT1	NM_003465.3	MANE Select	c.304G>A	p.Gly102Ser	missense	Exon 4 of 11	NP_003456.1
CHIT1	NR_045784.2		n.341G>A		non_coding_transcript_exon	Exon 4 of 13
CHIT1	NR_045785.2		n.341G>A		non_coding_transcript_exon	Exon 4 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.304G>A	p.Gly102Ser	missense	Exon 4 of 11	ENSP00000356198.1
CHIT1	ENST00000491855.5	TSL:1	n.304G>A		non_coding_transcript_exon	Exon 4 of 12	ENSP00000423778.1
CHIT1	ENST00000503786.1	TSL:1	n.304G>A		non_coding_transcript_exon	Exon 4 of 13	ENSP00000421617.1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45014

AN:

151466

Hom.:

6716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.299

GnomAD2 exomes

AF:

0.305

AC:

76573

AN:

251020

AF XY:

0.301

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.323

Gnomad EAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.298

GnomAD4 exome

AF:

0.301

AC:

440170

AN:

1460362

Hom.:

67051

Cov.:

AF XY:

0.300

AC XY:

218266

AN XY:

726572

show subpopulations

African (AFR)

AF:

0.264

AC:

8848

AN:

33462

American (AMR)

AF:

0.360

AC:

16091

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

8653

AN:

26120

East Asian (EAS)

AF:

0.285

AC:

11317

AN:

39680

South Asian (SAS)

AF:

0.264

AC:

22783

AN:

86208

European-Finnish (FIN)

AF:

0.318

AC:

16941

AN:

53342

Middle Eastern (MID)

AF:

0.242

AC:

1392

AN:

5758

European-Non Finnish (NFE)

AF:

0.303

AC:

336474

AN:

1110766

Other (OTH)

AF:

0.293

AC:

17671

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

16343

32685

49028

65370

81713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10984

21968

32952

43936

54920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.297

AC:

45064

AN:

151586

Hom.:

6729

Cov.:

AF XY:

0.298

AC XY:

22062

AN XY:

74026

show subpopulations

African (AFR)

AF:

0.270

AC:

11145

AN:

41270

American (AMR)

AF:

0.305

AC:

4643

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1160

AN:

3468

East Asian (EAS)

AF:

0.268

AC:

1370

AN:

5104

South Asian (SAS)

AF:

0.258

AC:

1241

AN:

4812

European-Finnish (FIN)

AF:

0.335

AC:

3516

AN:

10482

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.311

AC:

21095

AN:

67902

Other (OTH)

AF:

0.302

AC:

638

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1594

3187

4781

6374

7968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.304

Hom.:

28643

Bravo

AF:

0.294

TwinsUK

AF:

0.297

AC:

1103

ALSPAC

AF:

0.300

AC:

1157

ESP6500AA

AF:

0.270

AC:

1188

ESP6500EA

AF:

0.293

AC:

2522

ExAC

AF:

0.303

AC:

36751

Asia WGS

AF:

0.296

AC:

1026

AN:

3478

EpiCase

AF:

0.299

EpiControl

AF:

0.283

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:4Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2Other:1

GenomeConnect - Invitae Patient Insights Network

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 11-13-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Mar 10, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24060732, 19725875, 17000706)

Chitotriosidase deficiency

Benign:2Other:1

Dec 20, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 01, 2007

OMIM

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:literature only

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

PhyloP100

6.7

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.23

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.20

MPC

0.46

ClinPred

0.026

GERP RS

2.6

Varity_R

0.80

gMVP

0.72

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over