dbSNP rs368913199: CHIT1:c.*143A>G (chr1-203216746-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003465.3(CHIT1):c.*143A>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 0.0000382 in 1,125,886 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 2 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

CHIT1
NM_003465.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.171

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003465.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHIT1	NM_003465.3	MANE Select	c.*143A>G	3_prime_UTR	Exon 11 of 11	NP_003456.1	Q13231-1
CHIT1	NM_001256125.2		c.*143A>G	3_prime_UTR	Exon 10 of 10	NP_001243054.2	Q13231-4
CHIT1	NR_045784.2		n.1809A>G	non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.*143A>G	3_prime_UTR	Exon 11 of 11	ENSP00000356198.1	Q13231-1
CHIT1	ENST00000491855.5	TSL:1	n.*451A>G	non_coding_transcript_exon	Exon 12 of 12	ENSP00000423778.1	Q13231-2
CHIT1	ENST00000491855.5	TSL:1	n.*451A>G	3_prime_UTR	Exon 12 of 12	ENSP00000423778.1	Q13231-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.0000198

AC:

AN:

201534

AF XY:

0.0000361

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000663

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000378

GnomAD4 exome

AF:

0.0000308

AC:

AN:

973616

Hom.:

Cov.:

AF XY:

0.0000458

AC XY:

AN XY:

502386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23940

American (AMR)

AF:

0.00

AC:

AN:

40318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22772

East Asian (EAS)

AF:

0.0000826

AC:

AN:

36320

South Asian (SAS)

AF:

0.00

AC:

AN:

74302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42906

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3240

European-Non Finnish (NFE)

AF:

0.0000146

AC:

AN:

685522

Other (OTH)

AF:

0.000384

AC:

AN:

44296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41548

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Chitotriosidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

-0.17

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over