rs574174

Positions:

• chr20-3670047-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025220.5(ADAM33):​c.2241-410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 336,478 control chromosomes in the GnomAD database, including 6,311 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 0.20 (3098 hom., cov: 32)
  • Exomes 𝑓: 0.18 (3213 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.2241-410G>A		intron_variant		ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.2241-410G>A		intron_variant		1	NM_025220.5	ENSP00000348912.3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30097 AN: 152022 Hom.: 3098 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.178 AC: 32805 AN: 184338 Hom.: 3213 Cov.: 0 AF XY: 0.178 AC XY: 17462 AN XY: 97910

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.198 AC: 30125 AN: 152140 Hom.: 3098 Cov.: 32 AF XY: 0.200 AC XY: 14898 AN XY: 74352

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.184

Alfa AF: 0.185 Hom.: 2421

Bravo AF: 0.191

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs574174; hg19: chr20-3650694;