Genetic Variant ADAM33:c.178-421A>G (chr20-3677564-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025220.5(ADAM33):c.178-421A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,104 control chromosomes in the GnomAD database, including 41,242 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 0.74 ( 41242 hom., cov: 32)

Consequence

ADAM33
NM_025220.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.823

Publications

9 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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new If you want to explore the variant's impact on the transcript NM_025220.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 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.178-421A>G	intron	N/A	NP_079496.1	Q9BZ11-1
ADAM33	NM_001282447.3		c.178-421A>G	intron	N/A	NP_001269376.1	A2A2L3
ADAM33	NM_153202.4		c.178-421A>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.178-421A>G	intron	N/A	ENSP00000348912.3	Q9BZ11-1
ADAM33	ENST00000379861.8	TSL:1	c.178-421A>G	intron	N/A	ENSP00000369190.4	A2A2L3
ADAM33	ENST00000882045.1		c.178-421A>G	intron	N/A	ENSP00000552104.1

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

111858

AN:

151986

Hom.:

41228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.698

Gnomad AMI

AF:

0.787

Gnomad AMR

AF:

0.753

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.759

Gnomad OTH

AF:

0.733

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.736

AC:

111911

AN:

152104

Hom.:

41242

Cov.:

AF XY:

0.733

AC XY:

54535

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.697

AC:

28913

AN:

41492

American (AMR)

AF:

0.753

AC:

11510

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

2492

AN:

3472

East Asian (EAS)

AF:

0.781

AC:

4027

AN:

5158

South Asian (SAS)

AF:

0.717

AC:

3454

AN:

4820

European-Finnish (FIN)

AF:

0.702

AC:

7434

AN:

10592

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.759

AC:

51624

AN:

67974

Other (OTH)

AF:

0.734

AC:

1545

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1523

3046

4569

6092

7615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.752

Hom.:

98868

Bravo

AF:

0.742

Asia WGS

AF:

0.780

AC:

2714

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.9

(source)

DANN

Benign

0.44

PhyloP100

-0.82

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over