Genetic Variant CHIA:c.481-465T>G (chr1-111317216-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_201653.4(CHIA):c.481-465T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 167,524 control chromosomes in the GnomAD database, including 6,026 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 0.25 ( 5452 hom., cov: 32)

Exomes 𝑓: 0.25 ( 574 hom. )

Consequence

CHIA
NM_201653.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.342

Publications

7 publications found

Variant links:

Genes affected

CHIA (HGNC:17432): (chitinase acidic) The protein encoded by this gene degrades chitin, which is found in the cell wall of most fungi as well as in arthropods and some nematodes. The encoded protein can also stimulate interleukin 13 expression, and variations in this gene can lead to asthma susceptibility. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CHIA links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201653.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHIA	NM_201653.4	MANE Select	c.481-465T>G	intron	N/A	NP_970615.2
CHIA	NM_001258001.2		c.157-465T>G	intron	N/A	NP_001244930.1
CHIA	NM_001258003.2		c.157-465T>G	intron	N/A	NP_001244932.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHIA	ENST00000369740.6	TSL:1 MANE Select	c.481-465T>G	intron	N/A	ENSP00000358755.1
CHIA	ENST00000422815.5	TSL:1	c.313-465T>G	intron	N/A	ENSP00000387671.1
CHIA	ENST00000430615.1	TSL:1	c.157-465T>G	intron	N/A	ENSP00000391132.1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38110

AN:

151994

Hom.:

5455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.250

AC:

3854

AN:

15412

Hom.:

574

Cov.:

AF XY:

0.253

AC XY:

2068

AN XY:

8172

show subpopulations

African (AFR)

AF:

0.0867

AC:

AN:

392

American (AMR)

AF:

0.165

AC:

484

AN:

2932

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

AN:

214

East Asian (EAS)

AF:

0.274

AC:

414

AN:

1512

South Asian (SAS)

AF:

0.351

AC:

589

AN:

1676

European-Finnish (FIN)

AF:

0.230

AC:

AN:

278

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.266

AC:

2076

AN:

7796

Other (OTH)

AF:

0.226

AC:

134

AN:

594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

124

248

372

496

620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.250

AC:

38101

AN:

152112

Hom.:

5452

Cov.:

AF XY:

0.252

AC XY:

18767

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.125

AC:

5193

AN:

41512

American (AMR)

AF:

0.192

AC:

2942

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

1162

AN:

3472

East Asian (EAS)

AF:

0.339

AC:

1756

AN:

5174

South Asian (SAS)

AF:

0.382

AC:

1839

AN:

4810

European-Finnish (FIN)

AF:

0.321

AC:

3399

AN:

10574

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.307

AC:

20865

AN:

67962

Other (OTH)

AF:

0.244

AC:

515

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1400

2800

4201

5601

7001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<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:

0.286

Hom.:

10839

Bravo

AF:

0.231

Asia WGS

AF:

0.318

AC:

1108

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.4

(source)

DANN

Benign

0.47

PhyloP100

-0.34

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