20-3669066-A-G

Variant names:

• chr20-3669066-A-G
• rs628965
• NM_025220.5:c.2405-66T>C

Variant summary

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

The NM_025220.5(ADAM33):​c.2405-66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,556,760 control chromosomes in the GnomAD database, including 319,761 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 0.65 (31940 hom., cov: 31)
  • Exomes 𝑓: 0.64 (287821 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.2405-66T>C		intron_variant	Intron 21 of 21	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.2405-66T>C		intron_variant	Intron 21 of 21	1	NM_025220.5	ENSP00000348912.3

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98007 AN: 151406 Hom.: 31904 Cov.: 31

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 0.638 AC: 897199 AN: 1405236 Hom.: 287821 Cov.: 26 AF XY: 0.642 AC XY: 450848 AN XY: 702126

African (AFR) AF: 0.684 AC: 21892 AN: 32020

American (AMR) AF: 0.653 AC: 28971 AN: 44354

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 15597 AN: 25726

East Asian (EAS) AF: 0.604 AC: 23722 AN: 39264

South Asian (SAS) AF: 0.742 AC: 62928 AN: 84752

European-Finnish (FIN) AF: 0.617 AC: 32645 AN: 52878

Middle Eastern (MID) AF: 0.655 AC: 3574 AN: 5458

European-Non Finnish (NFE) AF: 0.631 AC: 670115 AN: 1062312

Other (OTH) AF: 0.646 AC: 37755 AN: 58472

GnomAD4 genome AF: 0.647 AC: 98093 AN: 151524 Hom.: 31940 Cov.: 31 AF XY: 0.647 AC XY: 47895 AN XY: 74000

African (AFR) AF: 0.677 AC: 27968 AN: 41296

American (AMR) AF: 0.673 AC: 10267 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2072 AN: 3460

East Asian (EAS) AF: 0.547 AC: 2790 AN: 5100

South Asian (SAS) AF: 0.725 AC: 3487 AN: 4812

European-Finnish (FIN) AF: 0.615 AC: 6462 AN: 10500

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 42877 AN: 67786

Other (OTH) AF: 0.652 AC: 1377 AN: 2112

Alfa AF: 0.642 Hom.: 4787

Bravo AF: 0.647

Asia WGS AF: 0.685 AC: 2379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.3
DANN	Benign	0.69
PhyloP100		-0.27
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: rs628965; hg19: chr20-3649713; COSMIC: COSV62937553;