Genetic Variant NM_003465.3:c.*534T>G (chr1-203216355-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 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 -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 VariationId 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.

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.*534T>G	3_prime_UTR	Exon 11 of 11	NP_003456.1	Q13231-1
CHIT1	NM_001256125.2		c.*534T>G	3_prime_UTR	Exon 10 of 10	NP_001243054.2	Q13231-4
CHIT1	NR_045784.2		n.2200T>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.*534T>G	3_prime_UTR	Exon 11 of 11	ENSP00000356198.1	Q13231-1
CHIT1	ENST00000479483.1	TSL:3	n.283+1384T>G	intron	N/A
CHIT1	ENST00000484834.5	TSL:2	n.5388+1384T>G	intron	N/A

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

GnomAD2 exomes

AF:

0.0154

AC:

2003

AN:

130214

AF XY:

0.0120

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 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

African (AFR)

AF:

0.226

AC:

1936

AN:

8554

American (AMR)

AF:

0.0157

AC:

427

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.00955

AC:

103

AN:

10786

East Asian (EAS)

AF:

0.00

AC:

AN:

9210

South Asian (SAS)

AF:

0.000821

AC:

AN:

59650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12366

Middle Eastern (MID)

AF:

0.0200

AC:

AN:

1150

European-Non Finnish (NFE)

AF:

0.000655

AC:

104

AN:

158776

Other (OTH)

AF:

0.0178

AC:

250

AN:

14042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

220

440

659

879

1099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.0657

AC:

10002

AN:

152206

Hom.:

1083

Cov.:

AF XY:

0.0633

AC XY:

4715

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.224

AC:

9309

AN:

41480

American (AMR)

AF:

0.0288

AC:

440

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00951

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00104

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00126

AC:

AN:

68018

Other (OTH)

AF:

0.0587

AC:

124

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

392

784

1175

1567

1959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0349

Hom.:

206

Bravo

AF:

0.0753

Asia WGS

AF:

0.0140

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

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

-0.89

CADD

Benign

0.51

(source)

DANN

Benign

0.41

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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