20-3675296-C-G

Variant names:

• chr20-3675296-C-G
• rs2787095
• NM_025220.5:c.255-191G>C

Variant summary

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

The NM_025220.5(ADAM33):​c.255-191G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,008 control chromosomes in the GnomAD database, including 18,179 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 0.45 (18179 hom., cov: 32)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.255-191G>C		intron_variant	Intron 3 of 21	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.255-191G>C		intron_variant	Intron 3 of 21	1	NM_025220.5	ENSP00000348912.3
ADAM33	ENST00000379861.8	c.255-191G>C		intron_variant	Intron 3 of 21	1		ENSP00000369190.4
ADAM33	ENST00000350009.6	c.255-191G>C		intron_variant	Intron 3 of 20	5		ENSP00000322550.5

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68755 AN: 151890 Hom.: 18177 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.452 AC: 68769 AN: 152008 Hom.: 18179 Cov.: 32 AF XY: 0.450 AC XY: 33409 AN XY: 74304

African (AFR) AF: 0.167 AC: 6938 AN: 41440

American (AMR) AF: 0.469 AC: 7164 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1984 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1980 AN: 5174

South Asian (SAS) AF: 0.613 AC: 2949 AN: 4810

European-Finnish (FIN) AF: 0.491 AC: 5191 AN: 10572

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40899 AN: 67958

Other (OTH) AF: 0.470 AC: 990 AN: 2108

Alfa AF: 0.388 Hom.: 1213

Bravo AF: 0.437

Asia WGS AF: 0.502 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.49
DANN	Benign	0.68
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2787095; hg19: chr20-3655943;