Genetic Variant ENST00000466620.5:n.2473A>G (chr20-3668493-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 ENST00000466620.5(ADAM33):n.2473A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 178,758 control chromosomes in the GnomAD database, including 417 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 0.063 ( 396 hom., cov: 32)

Exomes 𝑓: 0.025 ( 21 hom. )

Consequence

ADAM33
ENST00000466620.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.313

Publications

13 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:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5 link	c.*470A>G		3_prime_UTR_variant	Exon 22 of 22	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.*470A>G		3_prime_UTR_variant	Exon 22 of 22	1	NM_025220.5	ENSP00000348912.3		Q9BZ11-1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9630

AN:

152018

Hom.:

393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0939

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.0778

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0341

Gnomad OTH

AF:

0.0692

GnomAD4 exome

AF:

0.0254

AC:

675

AN:

26622

Hom.:

Cov.:

AF XY:

0.0260

AC XY:

362

AN XY:

13948

show subpopulations

African (AFR)

AF:

0.0867

AC:

AN:

946

American (AMR)

AF:

0.0446

AC:

124

AN:

2778

Ashkenazi Jewish (ASJ)

AF:

0.0155

AC:

AN:

580

East Asian (EAS)

AF:

0.0535

AC:

AN:

1812

South Asian (SAS)

AF:

0.0263

AC:

AN:

2012

European-Finnish (FIN)

AF:

0.0165

AC:

AN:

1090

Middle Eastern (MID)

AF:

0.0349

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0156

AC:

249

AN:

15980

Other (OTH)

AF:

0.0299

AC:

AN:

1338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0634

AC:

9642

AN:

152136

Hom.:

396

Cov.:

AF XY:

0.0653

AC XY:

4857

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.103

AC:

4261

AN:

41470

American (AMR)

AF:

0.0938

AC:

1433

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0352

AC:

122

AN:

3470

East Asian (EAS)

AF:

0.126

AC:

651

AN:

5168

South Asian (SAS)

AF:

0.0776

AC:

374

AN:

4818

European-Finnish (FIN)

AF:

0.0288

AC:

305

AN:

10600

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0341

AC:

2319

AN:

68014

Other (OTH)

AF:

0.0685

AC:

145

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

454

908

1363

1817

2271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0460

Hom.:

256

Bravo

AF:

0.0689

Asia WGS

AF:

0.100

AC:

347

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.9

(source)

DANN

Benign

0.77

PhyloP100

-0.31

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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