rs2297950

Positions:

chr1-203225058-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIT1	NM_003465.3 linkuse as main transcript	c.304G>A	p.Gly102Ser	missense_variant	4/11	ENST00000367229.6	NP_003456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000367229.6 linkuse as main transcript	c.304G>A	p.Gly102Ser	missense_variant	4/11	1	NM_003465.3	ENSP00000356198	P1	Q13231-1

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

GnomAD3 exomes

AF:

0.305

AC:

76573

AN:

251020

Hom.:

11856

AF XY:

0.301

AC XY:

40782

AN XY:

135684

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 SAS exome

AF:

0.267

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

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.331

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.297

AC:

45064

AN:

151586

Hom.:

6729

Cov.:

AF XY:

0.298

AC XY:

22062

AN XY:

74026

show subpopulations

Gnomad4 AFR

AF:

0.270

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.258

Gnomad4 FIN

AF:

0.335

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.302

Hom.:

13865

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 2020	This variant is associated with the following publications: (PMID: 24060732, 19725875, 17000706) -
not provided, no classification provided	phenotyping only	GenomeConnect - Invitae Patient Insights Network	-	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. -
Uncertain significance, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Chitotriosidase deficiency

Benign:2Other:1

Affects, no assertion criteria provided	literature only	OMIM	Sep 01, 2007	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

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

MutationTaster

Benign

0.0012

P;P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over