20-3668784-A-G

Variant names:

• chr20-3668784-A-G
• rs677044
• ENST00000466620.5:n.2182T>C

Variant summary

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

The ENST00000466620.5(ADAM33):​n.2182T>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 0.218 in 712,174 control chromosomes in the GnomAD database, including 17,916 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 0.24 (4780 hom., cov: 32)
  • Exomes 𝑓: 0.21 (13136 hom.)
• Consequence: ADAM33 ENST00000466620.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 24 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 (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.*179T>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.*179T>C		3_prime_UTR_variant	Exon 22 of 22	1	NM_025220.5	ENSP00000348912.3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36783 AN: 151822 Hom.: 4773 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.211 AC: 118401 AN: 560234 Hom.: 13136 Cov.: 6 AF XY: 0.210 AC XY: 63208 AN XY: 301034

African (AFR) AF: 0.313 AC: 4973 AN: 15906

American (AMR) AF: 0.177 AC: 6088 AN: 34464

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 4271 AN: 16670

East Asian (EAS) AF: 0.237 AC: 8035 AN: 33944

South Asian (SAS) AF: 0.199 AC: 11547 AN: 58160

European-Finnish (FIN) AF: 0.159 AC: 5520 AN: 34682

Middle Eastern (MID) AF: 0.226 AC: 499 AN: 2208

European-Non Finnish (NFE) AF: 0.212 AC: 70926 AN: 334280

Other (OTH) AF: 0.219 AC: 6542 AN: 29920

GnomAD4 genome AF: 0.242 AC: 36806 AN: 151940 Hom.: 4780 Cov.: 32 AF XY: 0.241 AC XY: 17900 AN XY: 74250

African (AFR) AF: 0.324 AC: 13422 AN: 41396

American (AMR) AF: 0.229 AC: 3501 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3466

East Asian (EAS) AF: 0.273 AC: 1406 AN: 5152

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4816

European-Finnish (FIN) AF: 0.146 AC: 1541 AN: 10562

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14354 AN: 67962

Other (OTH) AF: 0.238 AC: 501 AN: 2106

Alfa AF: 0.224 Hom.: 10043

Bravo AF: 0.253

Asia WGS AF: 0.211 AC: 736 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	2.2
DANN	Benign	0.48
PhyloP100		-0.18
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: rs677044; hg19: chr20-3649431; COSMIC: COSV62933840;