20-3671095-C-G

Variant names:

• chr20-3671095-C-G
• rs528557
• NM_025220.5:c.2151G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_025220.5(ADAM33):​c.2151G>C​(p.Gly717Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,593,178 control chromosomes in the GnomAD database, including 74,095 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 0.38 (12821 hom., cov: 34)
  • Exomes 𝑓: 0.28 (61274 hom.)
• Consequence: ADAM33 NM_025220.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 57 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=0.476 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025220.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	NM_025220.5	MANE Select	c.2151G>C	p.Gly717Gly	synonymous	Exon 19 of 22	NP_079496.1
	ADAM33	NM_001282447.3		c.2151G>C	p.Gly717Gly	synonymous	Exon 19 of 22	NP_001269376.1
	ADAM33	NM_153202.4		c.2073G>C	p.Gly691Gly	synonymous	Exon 18 of 21	NP_694882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.2151G>C	p.Gly717Gly	synonymous	Exon 19 of 22	ENSP00000348912.3
	ADAM33	ENST00000379861.8	TSL:1	c.2151G>C	p.Gly717Gly	synonymous	Exon 19 of 22	ENSP00000369190.4
	ADAM33	ENST00000466620.5	TSL:1	n.1712G>C		non_coding_transcript_exon	Exon 8 of 11

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57615 AN: 152016 Hom.: 12804 Cov.: 34

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.359

GnomAD2 exomes AF: 0.294 AC: 63195 AN: 214728 AF XY: 0.297

Gnomad AFR exome AF: 0.646

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.286

Gnomad EAS exome AF: 0.226

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.272

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.283 AC: 407690 AN: 1441044 Hom.: 61274 Cov.: 38 AF XY: 0.285 AC XY: 203946 AN XY: 715108

African (AFR) AF: 0.649 AC: 21485 AN: 33120

American (AMR) AF: 0.167 AC: 6918 AN: 41318

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7326 AN: 25704

East Asian (EAS) AF: 0.237 AC: 9214 AN: 38830

South Asian (SAS) AF: 0.362 AC: 30381 AN: 83816

European-Finnish (FIN) AF: 0.352 AC: 18088 AN: 51368

Middle Eastern (MID) AF: 0.361 AC: 1982 AN: 5492

European-Non Finnish (NFE) AF: 0.267 AC: 294285 AN: 1101832

Other (OTH) AF: 0.302 AC: 18011 AN: 59564

GnomAD4 genome AF: 0.379 AC: 57672 AN: 152134 Hom.: 12821 Cov.: 34 AF XY: 0.380 AC XY: 28266 AN XY: 74380

African (AFR) AF: 0.635 AC: 26372 AN: 41514

American (AMR) AF: 0.256 AC: 3920 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1192 AN: 5162

South Asian (SAS) AF: 0.348 AC: 1682 AN: 4832

European-Finnish (FIN) AF: 0.355 AC: 3763 AN: 10594

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18737 AN: 67950

Other (OTH) AF: 0.357 AC: 754 AN: 2110

Alfa AF: 0.227 Hom.: 777

Bravo AF: 0.376

Asia WGS AF: 0.289 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Benign	0.64
PhyloP100		0.48
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs528557; hg19: chr20-3651742; COSMIC: COSV62933823; COSMIC: COSV62933823;