Genetic Variant ADAM33:c.2405-74A>G (chr20-3669074-T-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.2405-74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,527,280 control chromosomes in the GnomAD database, including 313,565 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 0.65 ( 31992 hom., cov: 32)

Exomes 𝑓: 0.64 ( 281573 hom. )

Consequence

ADAM33
NM_025220.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.372

Publications

16 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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5 link	c.2405-74A>G		intron_variant	Intron 21 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.2405-74A>G		intron_variant	Intron 21 of 21	1	NM_025220.5	ENSP00000348912.3		Q9BZ11-1

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98115

AN:

151404

Hom.:

31958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.680

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.616

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.633

Gnomad OTH

AF:

0.648

GnomAD4 exome

AF:

0.638

AC:

877646

AN:

1375760

Hom.:

281573

Cov.:

AF XY:

0.642

AC XY:

442371

AN XY:

689352

show subpopulations

African (AFR)

AF:

0.684

AC:

21485

AN:

31388

American (AMR)

AF:

0.652

AC:

28874

AN:

44280

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

15472

AN:

25540

East Asian (EAS)

AF:

0.604

AC:

23634

AN:

39148

South Asian (SAS)

AF:

0.742

AC:

62366

AN:

84080

European-Finnish (FIN)

AF:

0.617

AC:

32530

AN:

52702

Middle Eastern (MID)

AF:

0.653

AC:

3528

AN:

5400

European-Non Finnish (NFE)

AF:

0.630

AC:

652735

AN:

1035806

Other (OTH)

AF:

0.645

AC:

37022

AN:

57416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

16259

32518

48778

65037

81296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16914

33828

50742

67656

84570

<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:

0.648

AC:

98198

AN:

151520

Hom.:

31992

Cov.:

AF XY:

0.648

AC XY:

47960

AN XY:

74002

show subpopulations

African (AFR)

AF:

0.680

AC:

28076

AN:

41292

American (AMR)

AF:

0.672

AC:

10253

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

2073

AN:

3462

East Asian (EAS)

AF:

0.547

AC:

2800

AN:

5122

South Asian (SAS)

AF:

0.725

AC:

3491

AN:

4812

European-Finnish (FIN)

AF:

0.616

AC:

6464

AN:

10502

Middle Eastern (MID)

AF:

0.658

AC:

192

AN:

292

European-Non Finnish (NFE)

AF:

0.633

AC:

42876

AN:

67764

Other (OTH)

AF:

0.651

AC:

1374

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1806

3611

5417

7222

9028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.642

Hom.:

6407

Bravo

AF:

0.648

Asia WGS

AF:

0.686

AC:

2384

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.6

(source)

DANN

Benign

0.62

PhyloP100

0.37

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