rs597980

Variant names:

• chr20-3670518-G-A
• rs597980
• NM_025220.5:c.2240+488C>T

Variant summary

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

The NM_025220.5(ADAM33):​c.2240+488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 161,438 control chromosomes in the GnomAD database, including 13,314 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 0.39 (12422 hom., cov: 33)
  • Exomes 𝑓: 0.42 (892 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 25 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 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.2240+488C>T		intron	N/A	NP_079496.1
	ADAM33	NM_001282447.3		c.2240+488C>T		intron	N/A	NP_001269376.1
	ADAM33	NM_153202.4		c.2162+488C>T		intron	N/A	NP_694882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.2240+488C>T		intron	N/A	ENSP00000348912.3
	ADAM33	ENST00000379861.8	TSL:1	c.2240+488C>T		intron	N/A	ENSP00000369190.4
	ADAM33	ENST00000466620.5	TSL:1	n.1801+488C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59302 AN: 151920 Hom.: 12409 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.416 AC: 3915 AN: 9400 Hom.: 892 Cov.: 0 AF XY: 0.430 AC XY: 2101 AN XY: 4884

African (AFR) AF: 0.136 AC: 25 AN: 184

American (AMR) AF: 0.464 AC: 909 AN: 1960

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 43 AN: 116

East Asian (EAS) AF: 0.248 AC: 108 AN: 436

South Asian (SAS) AF: 0.470 AC: 310 AN: 660

European-Finnish (FIN) AF: 0.288 AC: 49 AN: 170

Middle Eastern (MID) AF: 0.389 AC: 7 AN: 18

European-Non Finnish (NFE) AF: 0.423 AC: 2292 AN: 5418

Other (OTH) AF: 0.393 AC: 172 AN: 438

GnomAD4 genome AF: 0.390 AC: 59338 AN: 152038 Hom.: 12422 Cov.: 33 AF XY: 0.390 AC XY: 29010 AN XY: 74310

African (AFR) AF: 0.237 AC: 9820 AN: 41474

American (AMR) AF: 0.453 AC: 6921 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1643 AN: 5148

South Asian (SAS) AF: 0.502 AC: 2424 AN: 4824

European-Finnish (FIN) AF: 0.417 AC: 4412 AN: 10568

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31287 AN: 67964

Other (OTH) AF: 0.395 AC: 833 AN: 2110

Alfa AF: 0.427 Hom.: 2179

Bravo AF: 0.385

Asia WGS AF: 0.448 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.46
PhyloP100		-0.073
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: rs597980; hg19: chr20-3651165;