dbSNP rs2486958: CHIT1:c.915+100T>G (chr1-203219564-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003465.3(CHIT1):c.915+100T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,376,092 control chromosomes in the GnomAD database, including 204,971 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 23084 hom., cov: 32)

Exomes 𝑓: 0.53 ( 181887 hom. )

Consequence

CHIT1
NM_003465.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.264

Publications

5 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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIT1	NM_003465.3 link	c.915+100T>G		intron_variant	Intron 8 of 10	ENST00000367229.6	NP_003456.1	Q13231-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHIT1	ENST00000367229.6 link	c.915+100T>G		intron_variant	Intron 8 of 10	1	NM_003465.3	ENSP00000356198.1		Q13231-1

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82447

AN:

151998

Hom.:

23049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.530

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.534

AC:

653761

AN:

1223976

Hom.:

181887

Cov.:

AF XY:

0.538

AC XY:

333496

AN XY:

619670

show subpopulations

African (AFR)

AF:

0.520

AC:

14987

AN:

28802

American (AMR)

AF:

0.747

AC:

33114

AN:

44336

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

13922

AN:

24624

East Asian (EAS)

AF:

0.953

AC:

36753

AN:

38558

South Asian (SAS)

AF:

0.693

AC:

56112

AN:

80972

European-Finnish (FIN)

AF:

0.475

AC:

24816

AN:

52276

Middle Eastern (MID)

AF:

0.518

AC:

2722

AN:

5254

European-Non Finnish (NFE)

AF:

0.494

AC:

443160

AN:

896722

Other (OTH)

AF:

0.537

AC:

28175

AN:

52432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

16264

32527

48791

65054

81318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12070

24140

36210

48280

60350

<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:

0.543

AC:

82540

AN:

152116

Hom.:

23084

Cov.:

AF XY:

0.550

AC XY:

40932

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.530

AC:

21989

AN:

41484

American (AMR)

AF:

0.640

AC:

9791

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1938

AN:

3472

East Asian (EAS)

AF:

0.935

AC:

4847

AN:

5186

South Asian (SAS)

AF:

0.715

AC:

3454

AN:

4832

European-Finnish (FIN)

AF:

0.490

AC:

5184

AN:

10578

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.496

AC:

33714

AN:

67958

Other (OTH)

AF:

0.559

AC:

1180

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1915

3831

5746

7662

9577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.515

Hom.:

28541

Bravo

AF:

0.550

Asia WGS

AF:

0.810

AC:

2811

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

(source)

DANN

Benign

0.52

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over