Variant chr1-203216770-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003465.3(CHIT1):c.*119C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00964 in 1,357,118 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0071 ( 5 hom., cov: 33)

Exomes 𝑓: 0.010 ( 83 hom. )

Consequence

CHIT1
NM_003465.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.829

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHIT1	NM_003465.3 linkuse as main transcript	c.*119C>T		3_prime_UTR_variant	11/11	ENST00000367229.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIT1	ENST00000367229.6 linkuse as main transcript	c.*119C>T		3_prime_UTR_variant	11/11	1	NM_003465.3	P1	Q13231-1

Frequencies

GnomAD3 genomes

AF:

0.00715

AC:

1089

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.000579

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00932

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00788

AC:

1824

AN:

231418

Hom.:

AF XY:

0.00789

AC XY:

1002

AN XY:

127058

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.00935

Gnomad ASJ exome

AF:

0.00115

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00493

Gnomad FIN exome

AF:

0.00935

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00592

GnomAD4 exome

AF:

0.00995

AC:

11988

AN:

1204778

Hom.:

Cov.:

AF XY:

0.00977

AC XY:

5975

AN XY:

611284

show subpopulations

Gnomad4 AFR exome

AF:

0.00169

Gnomad4 AMR exome

AF:

0.00863

Gnomad4 ASJ exome

AF:

0.00132

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.00515

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.00591

GnomAD4 genome

AF:

0.00715

AC:

1089

AN:

152340

Hom.:

Cov.:

AF XY:

0.00675

AC XY:

503

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.000579

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00932

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00849

Hom.:

Bravo

AF:

0.00640

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Chitotriosidase deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.0

DANN

Benign

0.38

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