Genetic Variant NM_201653.4:c.56-57A>C (chr1-111312133-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_201653.4(CHIA):c.56-57A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,436,970 control chromosomes in the GnomAD database, including 707,229 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 0.96 ( 70494 hom., cov: 31)

Exomes 𝑓: 1.0 ( 636735 hom. )

Consequence

CHIA
NM_201653.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

4 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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	UniProt
CHIA	NM_201653.4	MANE Select	c.56-57A>C	intron	N/A	NP_970615.2	Q9BZP6-1
CHIA	NM_001258001.2		c.-68+415A>C	intron	N/A	NP_001244930.1	Q9BZP6-2
CHIA	NM_001258003.2		c.-68+415A>C	intron	N/A	NP_001244932.1	Q9BZP6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHIA	ENST00000369740.6	TSL:1 MANE Select	c.56-57A>C	intron	N/A	ENSP00000358755.1	Q9BZP6-1
CHIA	ENST00000422815.5	TSL:1	c.90-2407A>C	intron	N/A	ENSP00000387671.1	Q5VUV5
CHIA	ENST00000430615.1	TSL:1	c.-68+415A>C	intron	N/A	ENSP00000391132.1	Q9BZP6-2

Frequencies

GnomAD3 genomes

AF:

0.961

AC:

146128

AN:

152126

Hom.:

70462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.864

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.986

Gnomad ASJ

AF:

0.995

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.974

GnomAD4 exome

AF:

0.995

AC:

1278767

AN:

1284726

Hom.:

636735

AF XY:

0.996

AC XY:

644772

AN XY:

647394

show subpopulations

African (AFR)

AF:

0.856

AC:

25505

AN:

29796

American (AMR)

AF:

0.991

AC:

43988

AN:

44386

Ashkenazi Jewish (ASJ)

AF:

0.995

AC:

24800

AN:

24934

East Asian (EAS)

AF:

0.999

AC:

38762

AN:

38786

South Asian (SAS)

AF:

1.00

AC:

82450

AN:

82474

European-Finnish (FIN)

AF:

1.00

AC:

53039

AN:

53040

Middle Eastern (MID)

AF:

0.987

AC:

4416

AN:

4474

European-Non Finnish (NFE)

AF:

1.00

AC:

951997

AN:

952458

Other (OTH)

AF:

0.990

AC:

53810

AN:

54378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

278

556

833

1111

1389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17482

34964

52446

69928

87410

<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:

0.960

AC:

146211

AN:

152244

Hom.:

70494

Cov.:

AF XY:

0.962

AC XY:

71629

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.864

AC:

35847

AN:

41510

American (AMR)

AF:

0.986

AC:

15084

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.995

AC:

3451

AN:

3468

East Asian (EAS)

AF:

0.999

AC:

5184

AN:

5188

South Asian (SAS)

AF:

0.999

AC:

4814

AN:

4820

European-Finnish (FIN)

AF:

1.00

AC:

10612

AN:

10612

Middle Eastern (MID)

AF:

0.956

AC:

281

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67967

AN:

68026

Other (OTH)

AF:

0.974

AC:

2059

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

270

540

810

1080

1350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.979

Hom.:

3833

Bravo

AF:

0.955

Asia WGS

AF:

0.989

AC:

3440

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.55

(source)

DANN

Benign

0.54

PhyloP100

-1.1

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