chr1-203216965-G-C

Position:

chr1-203216965-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000367229.6(CHIT1):c.1325C>G(p.Ala442Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,614,100 control chromosomes in the GnomAD database, including 12,183 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A442V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.12 ( 1172 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11011 hom. )

Consequence

CHIT1
ENST00000367229.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0810

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=0.0013396144).

BP6

Variant 1-203216965-G-C is Benign according to our data. Variant chr1-203216965-G-C is described in ClinVar as [Benign]. Clinvar id is 294910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 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.1325C>G	p.Ala442Gly	missense_variant	11/11	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.1325C>G	p.Ala442Gly	missense_variant	11/11	1	NM_003465.3	ENSP00000356198	P1	Q13231-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18101

AN:

152126

Hom.:

1161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0998

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0637

Gnomad SAS

AF:

0.0972

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.131

GnomAD3 exomes

AF:

0.125

AC:

31316

AN:

251060

Hom.:

2107

AF XY:

0.122

AC XY:

16498

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.0704

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.120

AC:

175693

AN:

1461856

Hom.:

11011

Cov.:

AF XY:

0.120

AC XY:

86984

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0931

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.108

Gnomad4 EAS exome

AF:

0.0809

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.119

AC:

18150

AN:

152244

Hom.:

1172

Cov.:

AF XY:

0.121

AC XY:

9032

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.0640

Gnomad4 SAS

AF:

0.0965

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.108

Hom.:

686

Bravo

AF:

0.119

TwinsUK

AF:

0.121

AC:

447

ALSPAC

AF:

0.122

AC:

471

ESP6500AA

AF:

0.0992

AC:

437

ESP6500EA

AF:

0.112

AC:

963

ExAC

AF:

0.122

AC:

14852

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Chitotriosidase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
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. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.9

DANN

Benign

0.79

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.031

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.8

N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

2.1

N;N

REVEL

Benign

0.022

Sift

Benign

0.72

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.0

B;.

Vest4

0.015

MPC

0.093

ClinPred

0.00043

GERP RS

3.1

Varity_R

0.15

gMVP

0.27

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