rs612709

Positions:

• chr20-3671560-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.1905+21C>T		intron_variant		ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.1905+21C>T		intron_variant		1	NM_025220.5	ENSP00000348912.3
ADAM33	ENST00000379861.8	c.1905+21C>T		intron_variant		1		ENSP00000369190.4
ADAM33	ENST00000466620.5	n.1544+21C>T		intron_variant		1
ADAM33	ENST00000350009.6	c.1905+21C>T		intron_variant		5		ENSP00000322550.5

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

GnomAD3 exomes AF: 0.167 AC: 39383 AN: 235972 Hom.: 4289 AF XY: 0.164 AC XY: 21064 AN XY: 128618

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 SAS exome AF: 0.185

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

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.0938

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.166

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

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.212

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs612709; hg19: chr20-3652207; COSMIC: COSV62934036; COSMIC: COSV62934036;