rs597980

Positions:

• chr20-3670518-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.2240+488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 161,438 control chromosomes in the GnomAD database, including 13,314 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 0.39 (12422 hom., cov: 33)
  • Exomes 𝑓: 0.42 (892 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM33	NM_025220.5	c.2240+488C>T		intron_variant		ENST00000356518.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM33	ENST00000356518.7	c.2240+488C>T		intron_variant		1	NM_025220.5	P4

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59302 AN: 151920 Hom.: 12409 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.416 AC: 3915 AN: 9400 Hom.: 892 Cov.: 0 AF XY: 0.430 AC XY: 2101 AN XY: 4884

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.371

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.470

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.390 AC: 59338 AN: 152038 Hom.: 12422 Cov.: 33 AF XY: 0.390 AC XY: 29010 AN XY: 74310

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.395

Alfa AF: 0.427 Hom.: 2179

Bravo AF: 0.385

Asia WGS AF: 0.448 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.46

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: rs597980; hg19: chr20-3651165;