Variant 1-203216107-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003465.3(CHIT1):c.*782C>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 0.000599 in 454,072 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 0 hom. )

Consequence

CHIT1
NM_003465.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.527

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIT1	NM_003465.3 linkuse as main transcript	c.*782C>T		3_prime_UTR_variant	11/11	ENST00000367229.6	NP_003456.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000367229.6 linkuse as main transcript	c.*782C>T	3_prime_UTR_variant	11/11	1	NM_003465.3	ENSP00000356198	P1	Q13231-1
CHIT1	ENST00000479483.1 linkuse as main transcript	n.283+1632C>T	intron_variant, non_coding_transcript_variant		3
CHIT1	ENST00000484834.5 linkuse as main transcript	n.5388+1632C>T	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000523

AC:

AN:

127994

Hom.:

AF XY:

0.000528

AC XY:

AN XY:

70092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000164

Gnomad ASJ exome

AF:

0.00124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000939

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.000613

Gnomad OTH exome

AF:

0.000251

GnomAD4 exome

AF:

0.000630

AC:

190

AN:

301732

Hom.:

Cov.:

AF XY:

0.000657

AC XY:

113

AN XY:

171954

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000257

Gnomad4 ASJ exome

AF:

0.00121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.000323

Gnomad4 NFE exome

AF:

0.000605

Gnomad4 OTH exome

AF:

0.000570

GnomAD4 genome

AF:

0.000538

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000940

Hom.:

Bravo

AF:

0.000502

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Chitotriosidase deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.0

DANN

Benign

0.32

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