20-3670622-G-A

Variant names:

• chr20-3670622-G-A
• rs598418
• NM_025220.5:c.2240+384C>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+384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 207,454 control chromosomes in the GnomAD database, including 40,193 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 0.63 (30220 hom., cov: 33)
  • Exomes 𝑓: 0.59 (9973 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492
• Publications: 19 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 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+384C>T		intron	N/A	NP_079496.1
	ADAM33	NM_001282447.3		c.2240+384C>T		intron	N/A	NP_001269376.1
	ADAM33	NM_153202.4		c.2162+384C>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+384C>T		intron	N/A	ENSP00000348912.3
	ADAM33	ENST00000379861.8	TSL:1	c.2240+384C>T		intron	N/A	ENSP00000369190.4
	ADAM33	ENST00000466620.5	TSL:1	n.1801+384C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95491 AN: 151944 Hom.: 30188 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.594 AC: 32905 AN: 55390 Hom.: 9973 Cov.: 0 AF XY: 0.596 AC XY: 17124 AN XY: 28730

African (AFR) AF: 0.606 AC: 1251 AN: 2066

American (AMR) AF: 0.580 AC: 2427 AN: 4182

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 970 AN: 1658

East Asian (EAS) AF: 0.509 AC: 2120 AN: 4168

South Asian (SAS) AF: 0.699 AC: 2070 AN: 2962

European-Finnish (FIN) AF: 0.580 AC: 1420 AN: 2448

Middle Eastern (MID) AF: 0.648 AC: 149 AN: 230

European-Non Finnish (NFE) AF: 0.597 AC: 20515 AN: 34368

Other (OTH) AF: 0.599 AC: 1983 AN: 3308

GnomAD4 genome AF: 0.628 AC: 95569 AN: 152064 Hom.: 30220 Cov.: 33 AF XY: 0.627 AC XY: 46619 AN XY: 74322

African (AFR) AF: 0.639 AC: 26496 AN: 41488

American (AMR) AF: 0.622 AC: 9504 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2079 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2561 AN: 5156

South Asian (SAS) AF: 0.722 AC: 3485 AN: 4824

European-Finnish (FIN) AF: 0.612 AC: 6474 AN: 10574

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.630 AC: 42839 AN: 67948

Other (OTH) AF: 0.632 AC: 1337 AN: 2114

Alfa AF: 0.627 Hom.: 61000

Bravo AF: 0.623

Asia WGS AF: 0.666 AC: 2313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.7
DANN	Benign	0.71
PhyloP100		0.49
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: rs598418; hg19: chr20-3651269;