dbSNP rs598418: ADAM33:c.2240+384C>T (chr20-3670622-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.2240+384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 207,454 control chromosomes in the GnomAD database, including 40,193 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 0.63 ( 30220 hom., cov: 33)

Exomes 𝑓: 0.59 ( 9973 hom. )

Consequence

ADAM33
NM_025220.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.492

Publications

19 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 = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5 link	c.2240+384C>T		intron_variant	Intron 19 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.2240+384C>T		intron_variant	Intron 19 of 21	1	NM_025220.5	ENSP00000348912.3		Q9BZ11-1

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95491

AN:

151944

Hom.:

30188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.622

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.630

GnomAD4 exome

AF:

0.594

AC:

32905

AN:

55390

Hom.:

9973

Cov.:

AF XY:

0.596

AC XY:

17124

AN XY:

28730

show subpopulations

African (AFR)

AF:

0.606

AC:

1251

AN:

2066

American (AMR)

AF:

0.580

AC:

2427

AN:

4182

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

970

AN:

1658

East Asian (EAS)

AF:

0.509

AC:

2120

AN:

4168

South Asian (SAS)

AF:

0.699

AC:

2070

AN:

2962

European-Finnish (FIN)

AF:

0.580

AC:

1420

AN:

2448

Middle Eastern (MID)

AF:

0.648

AC:

149

AN:

230

European-Non Finnish (NFE)

AF:

0.597

AC:

20515

AN:

34368

Other (OTH)

AF:

0.599

AC:

1983

AN:

3308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

616

1232

1849

2465

3081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

226

452

678

904

1130

<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:

0.628

AC:

95569

AN:

152064

Hom.:

30220

Cov.:

AF XY:

0.627

AC XY:

46619

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.639

AC:

26496

AN:

41488

American (AMR)

AF:

0.622

AC:

9504

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

2079

AN:

3472

East Asian (EAS)

AF:

0.497

AC:

2561

AN:

5156

South Asian (SAS)

AF:

0.722

AC:

3485

AN:

4824

European-Finnish (FIN)

AF:

0.612

AC:

6474

AN:

10574

Middle Eastern (MID)

AF:

0.658

AC:

192

AN:

292

European-Non Finnish (NFE)

AF:

0.630

AC:

42839

AN:

67948

Other (OTH)

AF:

0.632

AC:

1337

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1862

3724

5586

7448

9310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.627

Hom.:

61000

Bravo

AF:

0.623

Asia WGS

AF:

0.666

AC:

2313

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

9.7

(source)

DANN

Benign

0.71

PhyloP100

0.49

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