dbSNP rs2280089: ADAM33:c.2332+66C>T (chr20-3669480-G-A) – 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.2332+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,538,446 control chromosomes in the GnomAD database, including 13,778 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 0.13 ( 1283 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12495 hom. )

Consequence

ADAM33
NM_025220.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.322

Publications

27 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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5 link	c.2332+66C>T		intron_variant	Intron 20 of 21	ENST00000356518.7	NP_079496.1	Q9BZ11-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7 link	c.2332+66C>T		intron_variant	Intron 20 of 21	1	NM_025220.5	ENSP00000348912.3		Q9BZ11-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19774

AN:

152014

Hom.:

1282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0966

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.132

AC:

182799

AN:

1386314

Hom.:

12495

Cov.:

AF XY:

0.134

AC XY:

91618

AN XY:

683884

show subpopulations

African (AFR)

AF:

0.114

AC:

3586

AN:

31566

American (AMR)

AF:

0.0721

AC:

2275

AN:

31572

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

3658

AN:

24218

East Asian (EAS)

AF:

0.113

AC:

4219

AN:

37426

South Asian (SAS)

AF:

0.175

AC:

13580

AN:

77544

European-Finnish (FIN)

AF:

0.174

AC:

8680

AN:

49820

Middle Eastern (MID)

AF:

0.200

AC:

1024

AN:

5132

European-Non Finnish (NFE)

AF:

0.129

AC:

138022

AN:

1071592

Other (OTH)

AF:

0.135

AC:

7755

AN:

57444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

7552

15105

22657

30210

37762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5012

10024

15036

20048

25060

<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:

0.130

AC:

19780

AN:

152132

Hom.:

1283

Cov.:

AF XY:

0.131

AC XY:

9724

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.116

AC:

4815

AN:

41502

American (AMR)

AF:

0.103

AC:

1574

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

500

AN:

3472

East Asian (EAS)

AF:

0.0969

AC:

499

AN:

5152

South Asian (SAS)

AF:

0.162

AC:

780

AN:

4826

European-Finnish (FIN)

AF:

0.166

AC:

1764

AN:

10602

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9363

AN:

67966

Other (OTH)

AF:

0.142

AC:

299

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

875

1749

2624

3498

4373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.130

Hom.:

1576

Bravo

AF:

0.120

Asia WGS

AF:

0.126

AC:

440

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over