20-3678284-C-T

Position:

• chr20-3678284-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025220.5(ADAM33):​c.178-1141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,182 control chromosomes in the GnomAD database, including 7,079 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 0.28 (7079 hom., cov: 34)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.178-1141G>A		intron_variant		ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.178-1141G>A		intron_variant		1	NM_025220.5	ENSP00000348912.3
ADAM33	ENST00000379861.8	c.178-1141G>A		intron_variant		1		ENSP00000369190.4
ADAM33	ENST00000350009.6	c.178-1141G>A		intron_variant		5		ENSP00000322550.5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43044 AN: 152064 Hom.: 7067 Cov.: 34

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.283 AC: 43088 AN: 152182 Hom.: 7079 Cov.: 34 AF XY: 0.281 AC XY: 20883 AN XY: 74394

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.267

Alfa AF: 0.216 Hom.: 4846

Bravo AF: 0.294

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs487377; hg19: chr20-3658931;