Genetic Variant ADAM33:c.2405-66T>C (chr20-3669066-A-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_025220.5(ADAM33):c.2405-66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,556,760 control chromosomes in the GnomAD database, including 319,761 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 0.65 ( 31940 hom., cov: 31)

Exomes 𝑓: 0.64 ( 287821 hom. )

Consequence

ADAM33
NM_025220.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.271

Publications

7 publications found

Variant links:

Genes affected

ADAM33 (HGNC:15478): (ADAM metallopeptidase domain 33) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This protein is a type I transmembrane protein implicated in asthma and bronchial hyperresponsiveness. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

ADAM33 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=-0.96).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025220.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAM33	NM_025220.5	MANE Select	c.2405-66T>C	intron	N/A	NP_079496.1	Q9BZ11-1
ADAM33	NM_001282447.3		c.2405-69T>C	intron	N/A	NP_001269376.1	A2A2L3
ADAM33	NM_153202.4		c.2327-66T>C	intron	N/A	NP_694882.1	Q9BZ11-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.2405-66T>C	intron	N/A	ENSP00000348912.3	Q9BZ11-1
ADAM33	ENST00000379861.8	TSL:1	c.2405-69T>C	intron	N/A	ENSP00000369190.4	A2A2L3
ADAM33	ENST00000466620.5	TSL:1	n.1966-66T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98007

AN:

151406

Hom.:

31904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.677

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.725

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.633

Gnomad OTH

AF:

0.649

GnomAD4 exome

AF:

0.638

AC:

897199

AN:

1405236

Hom.:

287821

Cov.:

AF XY:

0.642

AC XY:

450848

AN XY:

702126

show subpopulations

African (AFR)

AF:

0.684

AC:

21892

AN:

32020

American (AMR)

AF:

0.653

AC:

28971

AN:

44354

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

15597

AN:

25726

East Asian (EAS)

AF:

0.604

AC:

23722

AN:

39264

South Asian (SAS)

AF:

0.742

AC:

62928

AN:

84752

European-Finnish (FIN)

AF:

0.617

AC:

32645

AN:

52878

Middle Eastern (MID)

AF:

0.655

AC:

3574

AN:

5458

European-Non Finnish (NFE)

AF:

0.631

AC:

670115

AN:

1062312

Other (OTH)

AF:

0.646

AC:

37755

AN:

58472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

16647

33295

49942

66590

83237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17578

35156

52734

70312

87890

<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:

0.647

AC:

98093

AN:

151524

Hom.:

31940

Cov.:

AF XY:

0.647

AC XY:

47895

AN XY:

74000

show subpopulations

African (AFR)

AF:

0.677

AC:

27968

AN:

41296

American (AMR)

AF:

0.673

AC:

10267

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

2072

AN:

3460

East Asian (EAS)

AF:

0.547

AC:

2790

AN:

5100

South Asian (SAS)

AF:

0.725

AC:

3487

AN:

4812

European-Finnish (FIN)

AF:

0.615

AC:

6462

AN:

10500

Middle Eastern (MID)

AF:

0.658

AC:

192

AN:

292

European-Non Finnish (NFE)

AF:

0.633

AC:

42877

AN:

67786

Other (OTH)

AF:

0.652

AC:

1377

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1795

3590

5385

7180

8975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<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:

0.642

Hom.:

4787

Bravo

AF:

0.647

Asia WGS

AF:

0.685

AC:

2379

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.3

(source)

DANN

Benign

0.69

PhyloP100

-0.27

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