ENST00000466620.5:n.2452G>C

Variant names:

• chr20-3668514-C-G
• rs2787094
• ENST00000466620.5:n.2452G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000466620.5(ADAM33):​n.2452G>C variant causes a non coding transcript exon 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 ENST00000466620.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836
• Publications: 60 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.*449G>C		3_prime_UTR_variant	Exon 22 of 22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.*449G>C		3_prime_UTR_variant	Exon 22 of 22	1	NM_025220.5	ENSP00000348912.3

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

African (AFR) AF: 0.551 AC: 968 AN: 1758

American (AMR) AF: 0.833 AC: 2919 AN: 3506

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 853 AN: 1100

East Asian (EAS) AF: 0.615 AC: 1861 AN: 3024

South Asian (SAS) AF: 0.777 AC: 2453 AN: 3156

European-Finnish (FIN) AF: 0.679 AC: 1339 AN: 1972

Middle Eastern (MID) AF: 0.747 AC: 133 AN: 178

European-Non Finnish (NFE) AF: 0.773 AC: 20412 AN: 26394

Other (OTH) AF: 0.760 AC: 1742 AN: 2292

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

African (AFR) AF: 0.590 AC: 24416 AN: 41400

American (AMR) AF: 0.777 AC: 11869 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2703 AN: 3466

East Asian (EAS) AF: 0.624 AC: 3220 AN: 5160

South Asian (SAS) AF: 0.747 AC: 3599 AN: 4820

European-Finnish (FIN) AF: 0.640 AC: 6749 AN: 10546

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52678 AN: 67970

Other (OTH) AF: 0.737 AC: 1556 AN: 2110

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
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2787094; hg19: chr20-3649161;