rs2271511

Variant names:

• chr20-3673786-C-T
• rs2271511
• NM_025220.5:c.864G>A

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.864G>A​(p.Gly288Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,532,452 control chromosomes in the GnomAD database, including 30,692 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 (5049 hom., cov: 33)
  • Exomes 𝑓: 0.19 (25643 hom.)
• Consequence: ADAM33 NM_025220.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 9 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=-0.72).
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 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.864G>A	p.Gly288Gly	synonymous	Exon 9 of 22	NP_079496.1
	ADAM33	NM_001282447.3		c.864G>A	p.Gly288Gly	synonymous	Exon 9 of 22	NP_001269376.1
	ADAM33	NM_153202.4		c.864G>A	p.Gly288Gly	synonymous	Exon 9 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.864G>A	p.Gly288Gly	synonymous	Exon 9 of 22	ENSP00000348912.3
	ADAM33	ENST00000379861.8	TSL:1	c.864G>A	p.Gly288Gly	synonymous	Exon 9 of 22	ENSP00000369190.4
	ADAM33	ENST00000350009.6	TSL:5	c.864G>A	p.Gly288Gly	synonymous	Exon 9 of 21	ENSP00000322550.5

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36816 AN: 151998 Hom.: 5045 Cov.: 33

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.204 AC: 26659 AN: 130940 AF XY: 0.210

Gnomad AFR exome AF: 0.391

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.199

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.188 AC: 258912 AN: 1380340 Hom.: 25643 Cov.: 35 AF XY: 0.191 AC XY: 129862 AN XY: 680838

African (AFR) AF: 0.387 AC: 12223 AN: 31544

American (AMR) AF: 0.126 AC: 4395 AN: 35008

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 5482 AN: 24884

East Asian (EAS) AF: 0.196 AC: 7039 AN: 35916

South Asian (SAS) AF: 0.279 AC: 22029 AN: 79016

European-Finnish (FIN) AF: 0.212 AC: 7139 AN: 33712

Middle Eastern (MID) AF: 0.270 AC: 1526 AN: 5650

European-Non Finnish (NFE) AF: 0.174 AC: 187254 AN: 1076966

Other (OTH) AF: 0.205 AC: 11825 AN: 57644

GnomAD4 genome AF: 0.242 AC: 36845 AN: 152112 Hom.: 5049 Cov.: 33 AF XY: 0.242 AC XY: 18026 AN XY: 74384

African (AFR) AF: 0.383 AC: 15877 AN: 41482

American (AMR) AF: 0.174 AC: 2665 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1011 AN: 5164

South Asian (SAS) AF: 0.282 AC: 1362 AN: 4828

European-Finnish (FIN) AF: 0.204 AC: 2160 AN: 10610

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12314 AN: 67948

Other (OTH) AF: 0.249 AC: 527 AN: 2114

Alfa AF: 0.219 Hom.: 733

Bravo AF: 0.241

Asia WGS AF: 0.233 AC: 808 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.5
DANN	Benign	0.96
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2271511; hg19: chr20-3654433; COSMIC: COSV62934054; COSMIC: COSV62934054;