20-3679000-G-A

Position:

• chr20-3679000-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025220.5(ADAM33):​c.177+492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000605 in 152,044 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 0.00061 (0 hom., cov: 32)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM33	NM_025220.5	c.177+492C>T		intron_variant		ENST00000356518.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM33	ENST00000356518.7	c.177+492C>T		intron_variant		1	NM_025220.5	P4
ADAM33	ENST00000379861.8	c.177+492C>T		intron_variant		1		A2
ADAM33	ENST00000350009.6	c.177+492C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.000606 AC: 92 AN: 151926 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000839

Gnomad OTH AF: 0.000956

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000605 AC: 92 AN: 152044 Hom.: 0 Cov.: 32 AF XY: 0.000673 AC XY: 50 AN XY: 74328

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.000839

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.0000801 Hom.: 160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs570269; hg19: chr20-3659647;