Genetic Variant ADAM33:c.2240+427C>A (chr20-3670579-G-T) – 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.2240+427C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 174,642 control chromosomes in the GnomAD database, including 30,035 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 0.59 ( 26671 hom., cov: 33)

Exomes 𝑓: 0.53 ( 3364 hom. )

Consequence

ADAM33
NM_025220.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

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=-0.73).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 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.2240+427C>A	intron	N/A	NP_079496.1	Q9BZ11-1
ADAM33	NM_001282447.3		c.2240+427C>A	intron	N/A	NP_001269376.1	A2A2L3
ADAM33	NM_153202.4		c.2162+427C>A	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.2240+427C>A	intron	N/A	ENSP00000348912.3	Q9BZ11-1
ADAM33	ENST00000379861.8	TSL:1	c.2240+427C>A	intron	N/A	ENSP00000369190.4	A2A2L3
ADAM33	ENST00000466620.5	TSL:1	n.1801+427C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89629

AN:

151862

Hom.:

26636

Cov.:

show subpopulations

Gnomad AFR

AF:

0.601

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.667

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.596

Gnomad OTH

AF:

0.588

GnomAD4 exome

AF:

0.530

AC:

12017

AN:

22662

Hom.:

3364

Cov.:

AF XY:

0.535

AC XY:

6408

AN XY:

11982

show subpopulations

African (AFR)

AF:

0.513

AC:

347

AN:

676

American (AMR)

AF:

0.534

AC:

1470

AN:

2754

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

302

AN:

564

East Asian (EAS)

AF:

0.343

AC:

502

AN:

1462

South Asian (SAS)

AF:

0.611

AC:

732

AN:

1198

European-Finnish (FIN)

AF:

0.504

AC:

419

AN:

832

Middle Eastern (MID)

AF:

0.662

AC:

AN:

European-Non Finnish (NFE)

AF:

0.542

AC:

7503

AN:

13848

Other (OTH)

AF:

0.553

AC:

697

AN:

1260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

249

498

748

997

1246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.590

AC:

89710

AN:

151980

Hom.:

26671

Cov.:

AF XY:

0.588

AC XY:

43703

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.601

AC:

24927

AN:

41450

American (AMR)

AF:

0.589

AC:

9009

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1960

AN:

3472

East Asian (EAS)

AF:

0.384

AC:

1977

AN:

5148

South Asian (SAS)

AF:

0.666

AC:

3207

AN:

4816

European-Finnish (FIN)

AF:

0.582

AC:

6149

AN:

10562

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.596

AC:

40473

AN:

67936

Other (OTH)

AF:

0.588

AC:

1240

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1886

3772

5658

7544

9430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.575

Hom.:

14096

Bravo

AF:

0.585

Asia WGS

AF:

0.583

AC:

2026

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.4

(source)

DANN

Benign

0.87

PhyloP100

1.1

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