Genetic Variant 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:

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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 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.2332+66C>T	intron	N/A	NP_079496.1	Q9BZ11-1
ADAM33	NM_001282447.3		c.2332+66C>T	intron	N/A	NP_001269376.1	A2A2L3
ADAM33	NM_153202.4		c.2254+66C>T	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.2332+66C>T	intron	N/A	ENSP00000348912.3	Q9BZ11-1
ADAM33	ENST00000379861.8	TSL:1	c.2332+66C>T	intron	N/A	ENSP00000369190.4	A2A2L3
ADAM33	ENST00000466620.5	TSL:1	n.1893+66C>T	intron	N/A

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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