rs17548837

chr20-3668985-ATCTGGACT-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.29

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]

ACMG classification

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	UniProt
ADAM33	NM_025220.5	c.2412_2419del	p.Gln804HisfsTer13	frameshift_variant	22/22	ENST00000356518.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM33	ENST00000356518.7	c.2412_2419del	p.Gln804HisfsTer13	frameshift_variant	22/22	1	NM_025220.5	P4

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7513 AN: 152044 Hom.: 226 Cov.: 31

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

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

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.: 31 AF XY: 0.0509 AC XY: 3787 AN XY: 74356

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.: 31

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

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

Invitae

Dec 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17548837; hg19: chr20-3649632;