20-3679309-C-T

Variant names:

• chr20-3679309-C-T
• rs7354032
• NM_025220.5:c.177+183G>A

Variant summary

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

The NM_025220.5(ADAM33):​c.177+183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 151,748 control chromosomes in the GnomAD database, including 165 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 0.041 (165 hom., cov: 31)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0667 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	NM_025220.5	MANE Select	c.177+183G>A		intron	N/A	NP_079496.1
	ADAM33	NM_001282447.3		c.177+183G>A		intron	N/A	NP_001269376.1
	ADAM33	NM_153202.4		c.177+183G>A		intron	N/A	NP_694882.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM33	ENST00000356518.7	TSL:1 MANE Select	c.177+183G>A		intron	N/A	ENSP00000348912.3
	ADAM33	ENST00000379861.8	TSL:1	c.177+183G>A		intron	N/A	ENSP00000369190.4
	ADAM33	ENST00000882045.1		c.177+183G>A		intron	N/A	ENSP00000552104.1

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 6136 AN: 151630 Hom.: 159 Cov.: 31

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0338

Gnomad OTH AF: 0.0340

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

GnomAD4 genome AF: 0.0406 AC: 6166 AN: 151748 Hom.: 165 Cov.: 31 AF XY: 0.0395 AC XY: 2928 AN XY: 74164

African (AFR) AF: 0.0688 AC: 2840 AN: 41302

American (AMR) AF: 0.0224 AC: 342 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.0136 AC: 70 AN: 5142

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4800

European-Finnish (FIN) AF: 0.0324 AC: 342 AN: 10554

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0338 AC: 2296 AN: 67910

Other (OTH) AF: 0.0337 AC: 71 AN: 2108

Alfa AF: 0.0436 Hom.: 68

Bravo AF: 0.0412

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism

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: rs7354032; hg19: chr20-3659956;