NM_025220.5:c.2405-32C>A

Variant names:

• chr20-3669032-G-T
• rs543749
• NM_025220.5:c.2405-32C>A

Variant summary

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

The NM_025220.5(ADAM33):​c.2405-32C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,605,364 control chromosomes in the GnomAD database, including 17,633 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 0.18 (2862 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14771 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402
• Publications: 19 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 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.2405-32C>A		intron	N/A	NP_079496.1
	ADAM33	NM_001282447.3		c.2405-35C>A		intron	N/A	NP_001269376.1
	ADAM33	NM_153202.4		c.2327-32C>A		intron	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.2405-32C>A		intron	N/A	ENSP00000348912.3
	ADAM33	ENST00000379861.8	TSL:1	c.2405-35C>A		intron	N/A	ENSP00000369190.4
	ADAM33	ENST00000466620.5	TSL:1	n.1966-32C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27395 AN: 151952 Hom.: 2861 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.144 AC: 35443 AN: 246030 AF XY: 0.142

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.0976

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.136 AC: 197245 AN: 1453294 Hom.: 14771 Cov.: 32 AF XY: 0.136 AC XY: 98338 AN XY: 722930

African (AFR) AF: 0.304 AC: 10105 AN: 33204

American (AMR) AF: 0.126 AC: 5516 AN: 43804

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2655 AN: 25884

East Asian (EAS) AF: 0.138 AC: 5453 AN: 39460

South Asian (SAS) AF: 0.170 AC: 14511 AN: 85126

European-Finnish (FIN) AF: 0.170 AC: 9016 AN: 53150

Middle Eastern (MID) AF: 0.121 AC: 686 AN: 5660

European-Non Finnish (NFE) AF: 0.127 AC: 140742 AN: 1106930

Other (OTH) AF: 0.143 AC: 8561 AN: 60076

GnomAD4 genome AF: 0.180 AC: 27431 AN: 152070 Hom.: 2862 Cov.: 32 AF XY: 0.184 AC XY: 13697 AN XY: 74320

African (AFR) AF: 0.289 AC: 11986 AN: 41440

American (AMR) AF: 0.158 AC: 2412 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3470

East Asian (EAS) AF: 0.144 AC: 746 AN: 5166

South Asian (SAS) AF: 0.171 AC: 824 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1893 AN: 10596

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8743 AN: 67980

Other (OTH) AF: 0.162 AC: 342 AN: 2106

Alfa AF: 0.144 Hom.: 705

Bravo AF: 0.183

Asia WGS AF: 0.158 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.45
PhyloP100		0.40
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: rs543749; hg19: chr20-3649679; COSMIC: COSV62934897;