20-3669156-G-C

Variant names:

• chr20-3669156-G-C
• rs678881
• NM_025220.5:c.2404+143C>G

Variant summary

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

The NM_025220.5(ADAM33):​c.2404+143C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,186,952 control chromosomes in the GnomAD database, including 32,550 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 0.23 (4064 hom., cov: 29)
  • Exomes 𝑓: 0.23 (28486 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 13 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	NM_025220.5	MANE Select	c.2404+143C>G		intron	N/A	NP_079496.1	Q9BZ11-1
	ADAM33	NM_001282447.3		c.2404+143C>G		intron	N/A	NP_001269376.1	A2A2L3
	ADAM33	NM_153202.4		c.2326+143C>G		intron	N/A	NP_694882.1	Q9BZ11-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.2404+143C>G		intron	N/A	ENSP00000348912.3	Q9BZ11-1
	ADAM33	ENST00000379861.8	TSL:1	c.2404+143C>G		intron	N/A	ENSP00000369190.4	A2A2L3
	ADAM33	ENST00000466620.5	TSL:1	n.1965+143C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34060 AN: 150980 Hom.: 4057 Cov.: 29

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.230 AC: 238130 AN: 1035854 Hom.: 28486 Cov.: 14 AF XY: 0.227 AC XY: 119965 AN XY: 528940

African (AFR) AF: 0.248 AC: 5939 AN: 23950

American (AMR) AF: 0.131 AC: 4599 AN: 35060

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 5778 AN: 21760

East Asian (EAS) AF: 0.107 AC: 3916 AN: 36728

South Asian (SAS) AF: 0.156 AC: 11452 AN: 73510

European-Finnish (FIN) AF: 0.204 AC: 9954 AN: 48762

Middle Eastern (MID) AF: 0.206 AC: 993 AN: 4810

European-Non Finnish (NFE) AF: 0.249 AC: 185352 AN: 745530

Other (OTH) AF: 0.222 AC: 10147 AN: 45744

GnomAD4 genome AF: 0.226 AC: 34082 AN: 151098 Hom.: 4064 Cov.: 29 AF XY: 0.222 AC XY: 16366 AN XY: 73806

African (AFR) AF: 0.244 AC: 10033 AN: 41130

American (AMR) AF: 0.172 AC: 2617 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 927 AN: 3458

East Asian (EAS) AF: 0.130 AC: 657 AN: 5050

South Asian (SAS) AF: 0.163 AC: 780 AN: 4776

European-Finnish (FIN) AF: 0.183 AC: 1905 AN: 10410

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16458 AN: 67764

Other (OTH) AF: 0.225 AC: 472 AN: 2096

Alfa AF: 0.118 Hom.: 205

Bravo AF: 0.227

Asia WGS AF: 0.118 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.9
DANN	Benign	0.66
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs678881; hg19: chr20-3649803;