rs2853209

Variant names:

• chr20-3670825-T-A
• rs2853209
• NM_025220.5:c.2240+181A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025220.5(ADAM33):​c.2240+181A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,048 control chromosomes in the GnomAD database, including 14,055 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 0.42 (14055 hom., cov: 33)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.2240+181A>T		intron_variant	Intron 19 of 21	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.2240+181A>T		intron_variant	Intron 19 of 21	1	NM_025220.5	ENSP00000348912.3

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63144 AN: 151930 Hom.: 14038 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.423

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.416 AC: 63187 AN: 152048 Hom.: 14055 Cov.: 33 AF XY: 0.416 AC XY: 30925 AN XY: 74316

African (AFR) AF: 0.258 AC: 10685 AN: 41452

American (AMR) AF: 0.468 AC: 7151 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1596 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2260 AN: 5154

South Asian (SAS) AF: 0.559 AC: 2700 AN: 4828

European-Finnish (FIN) AF: 0.440 AC: 4662 AN: 10584

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32640 AN: 67956

Other (OTH) AF: 0.428 AC: 901 AN: 2106

Alfa AF: 0.437 Hom.: 1871

Bravo AF: 0.411

Asia WGS AF: 0.523 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2853209; hg19: chr20-3651472;