rs17513895

Positions:

• chr20-3674173-G-C

Variant summary

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

The NM_025220.5(ADAM33):​c.667-38C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,614,114 control chromosomes in the GnomAD database, including 436 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 0.032 (178 hom., cov: 33)
  • Exomes 𝑓: 0.012 (258 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM33	NM_025220.5	c.667-38C>G		intron_variant		ENST00000356518.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM33	ENST00000356518.7	c.667-38C>G		intron_variant		1	NM_025220.5	P4
ADAM33	ENST00000379861.8	c.667-38C>G		intron_variant		1		A2
ADAM33	ENST00000350009.6	c.667-38C>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4876 AN: 152146 Hom.: 176 Cov.: 33

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0283

GnomAD3 exomes AF: 0.0155 AC: 3906 AN: 251318 Hom.: 82 AF XY: 0.0139 AC XY: 1885 AN XY: 135868

Gnomad AFR exome AF: 0.0873

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.0424

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00480

Gnomad FIN exome AF: 0.00185

Gnomad NFE exome AF: 0.0112

Gnomad OTH exome AF: 0.0192

GnomAD4 exome AF: 0.0124 AC: 18158 AN: 1461850 Hom.: 258 Cov.: 35 AF XY: 0.0121 AC XY: 8825 AN XY: 727228

Gnomad4 AFR exome AF: 0.0914

Gnomad4 AMR exome AF: 0.0141

Gnomad4 ASJ exome AF: 0.0429

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00511

Gnomad4 FIN exome AF: 0.00170

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.0169

GnomAD4 genome AF: 0.0321 AC: 4886 AN: 152264 Hom.: 178 Cov.: 33 AF XY: 0.0305 AC XY: 2268 AN XY: 74444

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0237 Hom.: 14

Bravo AF: 0.0355

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.78

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: rs17513895; hg19: chr20-3654820;