dbSNP rs17513895: ADAM33:c.667-38C>G (chr20-3674173-G-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_025220.5(ADAM33):c.667-38C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,614,114 control chromosomes in the GnomAD database, including 436 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 0.032 ( 178 hom., cov: 33)

Exomes 𝑓: 0.012 ( 258 hom. )

Consequence

ADAM33
NM_025220.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0770

Publications

3 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=-0.71).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5 link	c.667-38C>G		intron_variant	Intron 7 of 21	ENST00000356518.7	NP_079496.1	Q9BZ11-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADAM33	ENST00000356518.7 link	c.667-38C>G	intron_variant	Intron 7 of 21	1	NM_025220.5	ENSP00000348912.3	Q9BZ11-1
ADAM33	ENST00000379861.8 link	c.667-38C>G	intron_variant	Intron 7 of 21	1		ENSP00000369190.4	A2A2L3
ADAM33	ENST00000350009.6 link	c.667-38C>G	intron_variant	Intron 7 of 20	5		ENSP00000322550.5	Q9BZ11-2

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4876

AN:

152146

Hom.:

176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0865

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0194

Gnomad ASJ

AF:

0.0395

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.0283

GnomAD2 exomes

AF:

0.0155

AC:

3906

AN:

251318

AF XY:

0.0139

show subpopulations

Gnomad AFR exome

AF:

0.0873

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0424

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.0192

GnomAD4 exome

AF:

0.0124

AC:

18158

AN:

1461850

Hom.:

258

Cov.:

AF XY:

0.0121

AC XY:

8825

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0914

AC:

3059

AN:

33480

American (AMR)

AF:

0.0141

AC:

630

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0429

AC:

1120

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00511

AC:

441

AN:

86258

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.0348

AC:

201

AN:

5768

European-Non Finnish (NFE)

AF:

0.0104

AC:

11593

AN:

1111994

Other (OTH)

AF:

0.0169

AC:

1023

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1269

2537

3806

5074

6343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.0321

AC:

4886

AN:

152264

Hom.:

178

Cov.:

AF XY:

0.0305

AC XY:

2268

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0865

AC:

3593

AN:

41538

American (AMR)

AF:

0.0194

AC:

297

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0395

AC:

137

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00684

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0108

AC:

733

AN:

68010

Other (OTH)

AF:

0.0280

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

238

475

713

950

1188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0237

Hom.:

Bravo

AF:

0.0355

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.077

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over