Genetic Variant ENST00000466620.5:n.2150C>T (chr20-3668816-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 ENST00000466620.5(ADAM33):n.2150C>T 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 0.0441 in 972,232 control chromosomes in the GnomAD database, including 1,401 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 0.060 ( 353 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1048 hom. )

Consequence

ADAM33
ENST00000466620.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

14 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5 link	c.*147C>T		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.*147C>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_025220.5	ENSP00000348912.3		Q9BZ11-1

Frequencies

GnomAD3 genomes

AF:

0.0605

AC:

9195

AN:

152078

Hom.:

354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0901

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0940

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.0614

Gnomad FIN

AF:

0.0289

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0355

Gnomad OTH

AF:

0.0584

GnomAD4 exome

AF:

0.0411

AC:

33666

AN:

820036

Hom.:

1048

Cov.:

AF XY:

0.0412

AC XY:

17711

AN XY:

429756

show subpopulations

African (AFR)

AF:

0.0838

AC:

1764

AN:

21058

American (AMR)

AF:

0.0812

AC:

3396

AN:

41824

Ashkenazi Jewish (ASJ)

AF:

0.0307

AC:

636

AN:

20710

East Asian (EAS)

AF:

0.132

AC:

4738

AN:

35832

South Asian (SAS)

AF:

0.0503

AC:

3478

AN:

69168

European-Finnish (FIN)

AF:

0.0288

AC:

1143

AN:

39636

Middle Eastern (MID)

AF:

0.0378

AC:

110

AN:

2912

European-Non Finnish (NFE)

AF:

0.0302

AC:

16594

AN:

549818

Other (OTH)

AF:

0.0462

AC:

1807

AN:

39078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

1072

2144

3217

4289

5361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

466

932

1398

1864

2330

<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:

0.0604

AC:

9196

AN:

152196

Hom.:

353

Cov.:

AF XY:

0.0618

AC XY:

4601

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0899

AC:

3732

AN:

41508

American (AMR)

AF:

0.0938

AC:

1434

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

122

AN:

3472

East Asian (EAS)

AF:

0.141

AC:

733

AN:

5182

South Asian (SAS)

AF:

0.0616

AC:

297

AN:

4820

European-Finnish (FIN)

AF:

0.0289

AC:

307

AN:

10612

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0355

AC:

2411

AN:

67998

Other (OTH)

AF:

0.0582

AC:

123

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

448

897

1345

1794

2242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0486

Hom.:

Bravo

AF:

0.0662

Asia WGS

AF:

0.0960

AC:

331

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.45

(source)

DANN

Benign

0.68

PhyloP100

-1.1

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