Genetic Variant CHIT1:c.*85G>A (chr1-203216804-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_003465.3(CHIT1):c.*85G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,576,016 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00074 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 30 hom. )

Consequence

CHIT1
NM_003465.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.25

Publications

3 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00154 (2188/1423686) while in subpopulation EAS AF = 0.0289 (1142/39490). AF 95% confidence interval is 0.0275. There are 30 homozygotes in GnomAdExome4. There are 1295 alleles in the male GnomAdExome4 subpopulation. Median coverage is 27. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 30 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.*85G>A	3_prime_UTR	Exon 11 of 11	NP_003456.1	Q13231-1
CHIT1	NM_001256125.2		c.*85G>A	3_prime_UTR	Exon 10 of 10	NP_001243054.2	Q13231-4
CHIT1	NR_045784.2		n.1751G>A	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.*85G>A	3_prime_UTR	Exon 11 of 11	ENSP00000356198.1	Q13231-1
CHIT1	ENST00000491855.5	TSL:1	n.*393G>A	non_coding_transcript_exon	Exon 12 of 12	ENSP00000423778.1	Q13231-2
CHIT1	ENST00000491855.5	TSL:1	n.*393G>A	3_prime_UTR	Exon 12 of 12	ENSP00000423778.1	Q13231-2

Frequencies

GnomAD3 genomes

AF:

0.000742

AC:

113

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0137

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00263

AC:

647

AN:

245888

AF XY:

0.00300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.0143

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000990

Gnomad OTH exome

AF:

0.00167

GnomAD4 exome

AF:

0.00154

AC:

2188

AN:

1423686

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1295

AN XY:

710204

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32620

American (AMR)

AF:

0.0000448

AC:

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.0000386

AC:

AN:

25894

East Asian (EAS)

AF:

0.0289

AC:

1142

AN:

39490

South Asian (SAS)

AF:

0.0101

AC:

853

AN:

84752

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52346

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.000106

AC:

115

AN:

1080890

Other (OTH)

AF:

0.00120

AC:

AN:

58954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

136

271

407

542

678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.000742

AC:

113

AN:

152330

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0137

AC:

AN:

5180

South Asian (SAS)

AF:

0.00786

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000180

Hom.:

Bravo

AF:

0.000510

Asia WGS

AF:

0.00953

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

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.36

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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