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. Variant has been reported in ClinVar as (no stars).

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.

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.667-38C>G	intron	N/A	NP_079496.1	Q9BZ11-1
ADAM33	NM_001282447.3		c.667-38C>G	intron	N/A	NP_001269376.1	A2A2L3
ADAM33	NM_153202.4		c.667-38C>G	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.667-38C>G	intron	N/A	ENSP00000348912.3	Q9BZ11-1
ADAM33	ENST00000379861.8	TSL:1	c.667-38C>G	intron	N/A	ENSP00000369190.4	A2A2L3
ADAM33	ENST00000882045.1		c.706-38C>G	intron	N/A	ENSP00000552104.1

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 v4.9

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

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