dbSNP rs2787093: ADAM33:c.*1148G>A (chr20-3667815-C-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.*1148G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,194 control chromosomes in the GnomAD database, including 57,506 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 0.87 ( 57461 hom., cov: 32)

Exomes 𝑓: 0.83 ( 45 hom. )

Consequence

ADAM33
NM_025220.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

Publications

7 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=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.905 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
ADAM33	NM_025220.5	MANE Select	c.*1148G>A	downstream_gene	N/A	NP_079496.1
ADAM33	NM_001282447.3		c.*1148G>A	downstream_gene	N/A	NP_001269376.1
ADAM33	NM_153202.4		c.*1148G>A	downstream_gene	N/A	NP_694882.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.*1148G>A	downstream_gene	N/A	ENSP00000348912.3
ADAM33	ENST00000379861.8	TSL:1	c.*1148G>A	downstream_gene	N/A	ENSP00000369190.4
ADAM33	ENST00000466620.5	TSL:1	n.*150G>A	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.868

AC:

131967

AN:

151950

Hom.:

57431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.852

Gnomad AMI

AF:

0.861

Gnomad AMR

AF:

0.917

Gnomad ASJ

AF:

0.874

Gnomad EAS

AF:

0.733

Gnomad SAS

AF:

0.906

Gnomad FIN

AF:

0.807

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.884

Gnomad OTH

AF:

0.882

GnomAD4 exome

AF:

0.833

AC:

105

AN:

126

Hom.:

AF XY:

0.824

AC XY:

AN XY:

102

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.950

AC:

AN:

European-Finnish (FIN)

AF:

0.889

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.792

AC:

AN:

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.868

AC:

132051

AN:

152068

Hom.:

57461

Cov.:

AF XY:

0.866

AC XY:

64344

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.852

AC:

35316

AN:

41452

American (AMR)

AF:

0.917

AC:

14029

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.874

AC:

3035

AN:

3472

East Asian (EAS)

AF:

0.733

AC:

3772

AN:

5144

South Asian (SAS)

AF:

0.905

AC:

4368

AN:

4826

European-Finnish (FIN)

AF:

0.807

AC:

8527

AN:

10572

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.884

AC:

60103

AN:

67990

Other (OTH)

AF:

0.880

AC:

1860

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

888

1776

2665

3553

4441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.880

Hom.:

11741

Bravo

AF:

0.875

Asia WGS

AF:

0.842

AC:

2927

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.3

(source)

DANN

Benign

0.75

PhyloP100

0.042

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over