rs3831317

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_003465.3(CHIT1):c.1049_1072dupAGGGACTGGGCGGGGCCATGGTCT(p.Val357_Trp358insTerGlyLeuGlyGlyAlaMetVal) variant causes a stop gained, conservative inframe insertion change. The variant allele was found at a frequency of 0.216 in 1,612,092 control chromosomes in the GnomAD database, including 43,887 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.18 ( 3446 hom., cov: 30)

Exomes 𝑓: 0.22 ( 40441 hom. )

Consequence

CHIT1
NM_003465.3 stop_gained, conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O:3

Conservation

PhyloP100: 6.53

Publications

22 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 -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_003465.3.

BP6

Variant 1-203217822-C-CAGACCATGGCCCCGCCCAGTCCCT is Benign according to our data. Variant chr1-203217822-C-CAGACCATGGCCCCGCCCAGTCCCT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 294920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIT1	NM_003465.3 link	c.1049_1072dupAGGGACTGGGCGGGGCCATGGTCT	p.Val357_Trp358insTerGlyLeuGlyGlyAlaMetVal	stop_gained, conservative_inframe_insertion	Exon 10 of 11	ENST00000367229.6	NP_003456.1	Q13231-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000367229.6 link	c.1049_1072dupAGGGACTGGGCGGGGCCATGGTCT	p.Val357_Trp358insTerGlyLeuGlyGlyAlaMetVal	stop_gained, conservative_inframe_insertion	Exon 10 of 11	1	NM_003465.3	ENSP00000356198.1		Q13231-1

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27698

AN:

151884

Hom.:

3436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0541

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.208

GnomAD4 exome

AF:

0.220

AC:

321217

AN:

1460092

Hom.:

40441

Cov.:

AF XY:

0.225

AC XY:

163467

AN XY:

726266

show subpopulations

African (AFR)

AF:

0.0446

AC:

1494

AN:

33476

American (AMR)

AF:

0.273

AC:

12179

AN:

44546

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5663

AN:

26106

East Asian (EAS)

AF:

0.562

AC:

22264

AN:

39594

South Asian (SAS)

AF:

0.396

AC:

34060

AN:

85974

European-Finnish (FIN)

AF:

0.180

AC:

9614

AN:

53280

Middle Eastern (MID)

AF:

0.242

AC:

1381

AN:

5696

European-Non Finnish (NFE)

AF:

0.199

AC:

220970

AN:

1111106

Other (OTH)

AF:

0.225

AC:

13592

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

13641

27282

40924

54565

68206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8080

16160

24240

32320

40400

<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:

0.182

AC:

27717

AN:

152000

Hom.:

3446

Cov.:

AF XY:

0.190

AC XY:

14127

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.0539

AC:

2241

AN:

41546

American (AMR)

AF:

0.261

AC:

3979

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

719

AN:

3464

East Asian (EAS)

AF:

0.573

AC:

2926

AN:

5104

South Asian (SAS)

AF:

0.428

AC:

2043

AN:

4778

European-Finnish (FIN)

AF:

0.179

AC:

1899

AN:

10590

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13279

AN:

67928

Other (OTH)

AF:

0.209

AC:

441

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1019

2039

3058

4078

5097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.166

Hom.:

305

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4Other:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Chitotriosidase deficiency

Benign:4Other:1

Jan 06, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 30, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely 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

- -

Nov 04, 2022

Revvity Omics, Revvity

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Other:2

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant classified as Benign and reported on 04-03-2023 by Invitae. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

GenomeConnect - GM1

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant classified as Benign and reported on 06-01-2022 by Invitae. GenomeConnect-GM1 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.5

Mutation Taster

=167/33

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over