20-3679000-G-C

Variant names:

• chr20-3679000-G-C
• rs570269
• NM_025220.5:c.177+492C>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.177+492C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,964 control chromosomes in the GnomAD database, including 12,210 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 0.35 (12210 hom., cov: 32)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.177+492C>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.177+492C>G		intron_variant	Intron 2 of 21	1	NM_025220.5	ENSP00000348912.3
ADAM33	ENST00000379861.8	c.177+492C>G		intron_variant	Intron 2 of 21	1		ENSP00000369190.4
ADAM33	ENST00000350009.6	c.177+492C>G		intron_variant	Intron 2 of 20	5		ENSP00000322550.5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53846 AN: 151846 Hom.: 12196 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.355 AC: 53912 AN: 151964 Hom.: 12210 Cov.: 32 AF XY: 0.355 AC XY: 26342 AN XY: 74280

African (AFR) AF: 0.618 AC: 25617 AN: 41418

American (AMR) AF: 0.341 AC: 5210 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3468

East Asian (EAS) AF: 0.623 AC: 3213 AN: 5160

South Asian (SAS) AF: 0.300 AC: 1446 AN: 4812

European-Finnish (FIN) AF: 0.199 AC: 2108 AN: 10574

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14215 AN: 67944

Other (OTH) AF: 0.366 AC: 774 AN: 2112

Alfa AF: 0.109 Hom.: 160

Bravo AF: 0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.69
DANN	Benign	0.37
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs570269; hg19: chr20-3659647;