rs612709

Variant names:

• chr20-3671560-G-A
• rs612709
• NM_025220.5:c.1905+21C>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.1905+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,606,960 control chromosomes in the GnomAD database, including 25,466 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 0.24 (6147 hom., cov: 33)
  • Exomes 𝑓: 0.15 (19319 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 41 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 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.1905+21C>T		intron	N/A	NP_079496.1	Q9BZ11-1
	ADAM33	NM_001282447.3		c.1905+21C>T		intron	N/A	NP_001269376.1	A2A2L3
	ADAM33	NM_153202.4		c.1905+21C>T		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.1905+21C>T		intron	N/A	ENSP00000348912.3	Q9BZ11-1
	ADAM33	ENST00000379861.8	TSL:1	c.1905+21C>T		intron	N/A	ENSP00000369190.4	A2A2L3
	ADAM33	ENST00000466620.5	TSL:1	n.1544+21C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36436 AN: 151990 Hom.: 6145 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.212

GnomAD2 exomes AF: 0.167 AC: 39383 AN: 235972 AF XY: 0.164

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.0882

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.139

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.151 AC: 220410 AN: 1454852 Hom.: 19319 Cov.: 36 AF XY: 0.151 AC XY: 109529 AN XY: 723316

African (AFR) AF: 0.504 AC: 16789 AN: 33324

American (AMR) AF: 0.0938 AC: 4105 AN: 43774

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4023 AN: 25964

East Asian (EAS) AF: 0.123 AC: 4833 AN: 39322

South Asian (SAS) AF: 0.182 AC: 15579 AN: 85736

European-Finnish (FIN) AF: 0.173 AC: 9020 AN: 52176

Middle Eastern (MID) AF: 0.159 AC: 914 AN: 5756

European-Non Finnish (NFE) AF: 0.140 AC: 155146 AN: 1108726

Other (OTH) AF: 0.166 AC: 10001 AN: 60074

GnomAD4 genome AF: 0.240 AC: 36478 AN: 152108 Hom.: 6147 Cov.: 33 AF XY: 0.239 AC XY: 17788 AN XY: 74366

African (AFR) AF: 0.487 AC: 20192 AN: 41466

American (AMR) AF: 0.146 AC: 2226 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3468

East Asian (EAS) AF: 0.127 AC: 655 AN: 5170

South Asian (SAS) AF: 0.181 AC: 874 AN: 4824

European-Finnish (FIN) AF: 0.181 AC: 1916 AN: 10586

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9515 AN: 67978

Other (OTH) AF: 0.212 AC: 449 AN: 2116

Alfa AF: 0.202 Hom.: 997

Bravo AF: 0.247

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs612709; hg19: chr20-3652207; COSMIC: COSV62934036; COSMIC: COSV62934036;