dbSNP rs3820145: CHIT1:c.605+126A>G (chr1-203223009-T-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.605+126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,270,640 control chromosomes in the GnomAD database, including 26,534 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 0.21 ( 3389 hom., cov: 32)

Exomes 𝑓: 0.20 ( 23145 hom. )

Consequence

CHIT1
NM_003465.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0620

Publications

7 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 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.605+126A>G	intron	N/A	NP_003456.1	Q13231-1
CHIT1	NM_001256125.2		c.548+126A>G	intron	N/A	NP_001243054.2	Q13231-4
CHIT1	NR_045784.2		n.642+126A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHIT1	ENST00000367229.6	TSL:1 MANE Select	c.605+126A>G	intron	N/A	ENSP00000356198.1	Q13231-1
CHIT1	ENST00000491855.5	TSL:1	n.605+126A>G	intron	N/A	ENSP00000423778.1	Q13231-2
CHIT1	ENST00000503786.1	TSL:1	n.605+126A>G	intron	N/A	ENSP00000421617.1	D6REY1

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31742

AN:

151958

Hom.:

3389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.193

GnomAD4 exome

AF:

0.197

AC:

220811

AN:

1118564

Hom.:

23145

AF XY:

0.196

AC XY:

112135

AN XY:

571316

show subpopulations

African (AFR)

AF:

0.226

AC:

6128

AN:

27140

American (AMR)

AF:

0.291

AC:

12841

AN:

44154

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5197

AN:

24002

East Asian (EAS)

AF:

0.333

AC:

12659

AN:

37986

South Asian (SAS)

AF:

0.186

AC:

14661

AN:

79028

European-Finnish (FIN)

AF:

0.191

AC:

7513

AN:

39334

Middle Eastern (MID)

AF:

0.176

AC:

902

AN:

5124

European-Non Finnish (NFE)

AF:

0.186

AC:

150894

AN:

812310

Other (OTH)

AF:

0.202

AC:

10016

AN:

49486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

9544

19089

28633

38178

47722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4652

9304

13956

18608

23260

<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:

0.209

AC:

31750

AN:

152076

Hom.:

3389

Cov.:

AF XY:

0.210

AC XY:

15608

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.226

AC:

9373

AN:

41460

American (AMR)

AF:

0.232

AC:

3543

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

782

AN:

3472

East Asian (EAS)

AF:

0.322

AC:

1657

AN:

5142

South Asian (SAS)

AF:

0.189

AC:

909

AN:

4818

European-Finnish (FIN)

AF:

0.190

AC:

2016

AN:

10590

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12916

AN:

67978

Other (OTH)

AF:

0.192

AC:

406

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1284

2568

3853

5137

6421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.200

Hom.:

2304

Bravo

AF:

0.213

Asia WGS

AF:

0.262

AC:

906

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.62

(source)

DANN

Benign

0.51

PhyloP100

0.062

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over