20-3670579-G-T

Position:

• chr20-3670579-G-T

Variant summary

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

The NM_025220.5(ADAM33):​c.2240+427C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 174,642 control chromosomes in the GnomAD database, including 30,035 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 0.59 (26671 hom., cov: 33)
  • Exomes 𝑓: 0.53 (3364 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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]

ADAM33 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.2240+427C>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.2240+427C>A		intron_variant		1	NM_025220.5	ENSP00000348912.3

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89629 AN: 151862 Hom.: 26636 Cov.: 33

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.530 AC: 12017 AN: 22662 Hom.: 3364 Cov.: 0 AF XY: 0.535 AC XY: 6408 AN XY: 11982

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.590 AC: 89710 AN: 151980 Hom.: 26671 Cov.: 33 AF XY: 0.588 AC XY: 43703 AN XY: 74270

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.588

Alfa AF: 0.553 Hom.: 3514

Bravo AF: 0.585

Asia WGS AF: 0.583 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.4
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs44707; hg19: chr20-3651226;