rs2787094

Positions:

• chr20-3668514-C-G

Variant summary

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

The NM_025220.5(ADAM33):​c.*449G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 195,328 control chromosomes in the GnomAD database, including 51,272 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 0.71 (38791 hom., cov: 30)
  • Exomes 𝑓: 0.75 (12481 hom.)
• Consequence: ADAM33 NM_025220.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.*449G>C		3_prime_UTR_variant	22/22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.*449G>C		3_prime_UTR_variant	22/22	1	NM_025220.5	ENSP00000348912	P4

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107651 AN: 151830 Hom.: 38776 Cov.: 30

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.753 AC: 32680 AN: 43380 Hom.: 12481 Cov.: 0 AF XY: 0.756 AC XY: 17186 AN XY: 22740

Gnomad4 AFR exome AF: 0.551

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 0.615

Gnomad4 SAS exome AF: 0.777

Gnomad4 FIN exome AF: 0.679

Gnomad4 NFE exome AF: 0.773

Gnomad4 OTH exome AF: 0.760

GnomAD4 genome AF: 0.709 AC: 107714 AN: 151948 Hom.: 38791 Cov.: 30 AF XY: 0.704 AC XY: 52296 AN XY: 74264

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.737

Alfa AF: 0.744 Hom.: 5255

Bravo AF: 0.713

Asia WGS AF: 0.681 AC: 2369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.65

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: rs2787094; hg19: chr20-3649161;