chr20-3670579-G-C

Variant names:

• chr20-3670579-G-C
• rs44707
• NM_025220.5:c.2240+427C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025220.5(ADAM33):​c.2240+427C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,920 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 27 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	NM_025220.5	MANE Select	c.2240+427C>G		intron	N/A	NP_079496.1	Q9BZ11-1
	ADAM33	NM_001282447.3		c.2240+427C>G		intron	N/A	NP_001269376.1	A2A2L3
	ADAM33	NM_153202.4		c.2162+427C>G		intron	N/A	NP_694882.1	Q9BZ11-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.2240+427C>G		intron	N/A	ENSP00000348912.3	Q9BZ11-1
	ADAM33	ENST00000379861.8	TSL:1	c.2240+427C>G		intron	N/A	ENSP00000369190.4	A2A2L3
	ADAM33	ENST00000466620.5	TSL:1	n.1801+427C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151920 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 22780 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12050

African (AFR) AF: 0.00 AC: 0 AN: 678

American (AMR) AF: 0.00 AC: 0 AN: 2774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 564

East Asian (EAS) AF: 0.00 AC: 0 AN: 1476

South Asian (SAS) AF: 0.00 AC: 0 AN: 1200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 70

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 13924

Other (OTH) AF: 0.00 AC: 0 AN: 1260

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151920 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74186

African (AFR) AF: 0.0000242 AC: 1 AN: 41352

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 14096

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.50
DANN	Benign	0.84
PhyloP100		1.1

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: rs44707; hg19: chr20-3651226;