Variant chr20-3668985-ATCTGGACT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_025220.5(ADAM33):c.2412_2419del(p.Gln804HisfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,606,126 control chromosomes in the GnomAD database, including 1,712 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 225 hom., cov: 31)

Exomes 𝑓: 0.038 ( 1487 hom. )

Consequence

ADAM33
NM_025220.5 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.29

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 20-3668985-ATCTGGACT-A is Benign according to our data. Variant chr20-3668985-ATCTGGACT-A is described in ClinVar as [Benign]. Clinvar id is 402342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5 linkuse as main transcript	c.2412_2419del	p.Gln804HisfsTer13	frameshift_variant	22/22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7 linkuse as main transcript	c.2412_2419del	p.Gln804HisfsTer13	frameshift_variant	22/22	1	NM_025220.5	ENSP00000348912	P4	Q9BZ11-1

Frequencies

GnomAD3 genomes

AF:

0.0494

AC:

7513

AN:

152044

Hom.:

226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0851

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0573

Gnomad FIN

AF:

0.0289

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0352

Gnomad OTH

AF:

0.0502

GnomAD3 exomes

AF:

0.0420

AC:

10285

AN:

245048

Hom.:

476

AF XY:

0.0394

AC XY:

5212

AN XY:

132298

show subpopulations

Gnomad AFR exome

AF:

0.0520

Gnomad AMR exome

AF:

0.0693

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.0371

Gnomad FIN exome

AF:

0.0222

Gnomad NFE exome

AF:

0.0293

Gnomad OTH exome

AF:

0.0342

GnomAD4 exome

AF:

0.0382

AC:

55572

AN:

1453964

Hom.:

1487

AF XY:

0.0384

AC XY:

27747

AN XY:

723178

show subpopulations

Gnomad4 AFR exome

AF:

0.0521

Gnomad4 AMR exome

AF:

0.0788

Gnomad4 ASJ exome

AF:

0.0315

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.0485

Gnomad4 FIN exome

AF:

0.0288

Gnomad4 NFE exome

AF:

0.0331

Gnomad4 OTH exome

AF:

0.0435

GnomAD4 genome

AF:

0.0494

AC:

7517

AN:

152162

Hom.:

225

Cov.:

AF XY:

0.0509

AC XY:

3787

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0576

Gnomad4 AMR

AF:

0.0849

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.0575

Gnomad4 FIN

AF:

0.0289

Gnomad4 NFE

AF:

0.0352

Gnomad4 OTH

AF:

0.0520

Alfa

AF:

0.0414

Hom.:

Bravo

AF:

0.0534

Asia WGS

AF:

0.0820

AC:

284

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 486/12518=3.8%. Frequency in 1000Genomes: 165/2178= 7.5% -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over