20-3677564-T-C

Variant names:

• chr20-3677564-T-C
• rs2853210
• NM_025220.5:c.178-421A>G

Variant summary

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

The NM_025220.5(ADAM33):​c.178-421A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,104 control chromosomes in the GnomAD database, including 41,242 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 0.74 (41242 hom., cov: 32)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.178-421A>G		intron_variant	Intron 2 of 21	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.178-421A>G		intron_variant	Intron 2 of 21	1	NM_025220.5	ENSP00000348912.3
ADAM33	ENST00000379861.8	c.178-421A>G		intron_variant	Intron 2 of 21	1		ENSP00000369190.4
ADAM33	ENST00000350009.6	c.178-421A>G		intron_variant	Intron 2 of 20	5		ENSP00000322550.5

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111858 AN: 151986 Hom.: 41228 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.736 AC: 111911 AN: 152104 Hom.: 41242 Cov.: 32 AF XY: 0.733 AC XY: 54535 AN XY: 74358

African (AFR) AF: 0.697 AC: 28913 AN: 41492

American (AMR) AF: 0.753 AC: 11510 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2492 AN: 3472

East Asian (EAS) AF: 0.781 AC: 4027 AN: 5158

South Asian (SAS) AF: 0.717 AC: 3454 AN: 4820

European-Finnish (FIN) AF: 0.702 AC: 7434 AN: 10592

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51624 AN: 67974

Other (OTH) AF: 0.734 AC: 1545 AN: 2104

Alfa AF: 0.752 Hom.: 98868

Bravo AF: 0.742

Asia WGS AF: 0.780 AC: 2714 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	1.9
DANN	Benign	0.44
PhyloP100		-0.82
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: rs2853210; hg19: chr20-3658211;