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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIT1	NM_003465.3 link	c.605+126A>G		intron_variant	Intron 6 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.605+126A>G		intron_variant	Intron 6 of 10	1	NM_003465.3	ENSP00000356198.1		Q13231-1

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

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

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 v4.3

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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rs3820145

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