20-3667731-A-G

Variant names:

• chr20-3667731-A-G
• rs512625
• NM_025220.5:c.*1232T>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.*1232T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,118 control chromosomes in the GnomAD database, including 40,999 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 0.73 (40999 hom., cov: 32)
• Consequence: ADAM33 NM_025220.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.994
• Publications: 22 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025220.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	NM_025220.5	MANE Select	c.*1232T>C		downstream_gene	N/A	NP_079496.1
	ADAM33	NM_001282447.3		c.*1232T>C		downstream_gene	N/A	NP_001269376.1
	ADAM33	NM_153202.4		c.*1232T>C		downstream_gene	N/A	NP_694882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.*1232T>C		downstream_gene	N/A	ENSP00000348912.3
	ADAM33	ENST00000379861.8	TSL:1	c.*1232T>C		downstream_gene	N/A	ENSP00000369190.4
	ADAM33	ENST00000466620.5	TSL:1	n.*234T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110943 AN: 151998 Hom.: 40973 Cov.: 32

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.730 AC: 111027 AN: 152118 Hom.: 40999 Cov.: 32 AF XY: 0.724 AC XY: 53812 AN XY: 74356

African (AFR) AF: 0.837 AC: 34717 AN: 41502

American (AMR) AF: 0.755 AC: 11541 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2542 AN: 3470

East Asian (EAS) AF: 0.629 AC: 3240 AN: 5154

South Asian (SAS) AF: 0.714 AC: 3446 AN: 4826

European-Finnish (FIN) AF: 0.562 AC: 5933 AN: 10562

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47260 AN: 67992

Other (OTH) AF: 0.743 AC: 1570 AN: 2114

Alfa AF: 0.714 Hom.: 117477

Bravo AF: 0.749

Asia WGS AF: 0.714 AC: 2486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.7
DANN	Benign	0.65
PhyloP100		0.99

Splicing

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

Other links and lift over

dbSNP: rs512625; hg19: chr20-3648378;