Variant chr1-203216355-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003465.3(CHIT1):c.*534T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 454,014 control chromosomes in the GnomAD database, including 1,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.066 ( 1083 hom., cov: 33)

Exomes 𝑓: 0.0096 ( 210 hom. )

Consequence

CHIT1
NM_003465.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.972

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-203216355-A-C is Benign according to our data. Variant chr1-203216355-A-C is described in ClinVar as [Benign]. Clinvar id is 294902.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHIT1	NM_003465.3 linkuse as main transcript	c.*534T>G		3_prime_UTR_variant	11/11	ENST00000367229.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHIT1	ENST00000367229.6 linkuse as main transcript	c.*534T>G	3_prime_UTR_variant	11/11	1	NM_003465.3	P1	Q13231-1
CHIT1	ENST00000479483.1 linkuse as main transcript	n.283+1384T>G	intron_variant, non_coding_transcript_variant		3
CHIT1	ENST00000484834.5 linkuse as main transcript	n.5388+1384T>G	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0655

AC:

9959

AN:

152088

Hom.:

1075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0288

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.0588

GnomAD3 exomes

AF:

0.0154

AC:

2003

AN:

130214

Hom.:

145

AF XY:

0.0120

AC XY:

854

AN XY:

71096

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.0161

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000670

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00999

GnomAD4 exome

AF:

0.00958

AC:

2892

AN:

301808

Hom.:

210

Cov.:

AF XY:

0.00723

AC XY:

1243

AN XY:

172006

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.00955

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000821

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000655

Gnomad4 OTH exome

AF:

0.0178

GnomAD4 genome

AF:

0.0657

AC:

10002

AN:

152206

Hom.:

1083

Cov.:

AF XY:

0.0633

AC XY:

4715

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.0288

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.0587

Alfa

AF:

0.0400

Hom.:

154

Bravo

AF:

0.0753

Asia WGS

AF:

0.0140

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Chitotriosidase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.51

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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