rs3918400

Positions:

• chr20-3668816-G-A

Variant summary

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

The NM_025220.5(ADAM33):​c.*147C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 972,232 control chromosomes in the GnomAD database, including 1,401 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 0.060 (353 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1048 hom.)
• Consequence: ADAM33 NM_025220.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.*147C>T		3_prime_UTR_variant	22/22	ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.*147C>T		3_prime_UTR_variant	22/22	1	NM_025220.5	ENSP00000348912	P4

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9195 AN: 152078 Hom.: 354 Cov.: 32

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0584

GnomAD4 exome AF: 0.0411 AC: 33666 AN: 820036 Hom.: 1048 Cov.: 11 AF XY: 0.0412 AC XY: 17711 AN XY: 429756

Gnomad4 AFR exome AF: 0.0838

Gnomad4 AMR exome AF: 0.0812

Gnomad4 ASJ exome AF: 0.0307

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0503

Gnomad4 FIN exome AF: 0.0288

Gnomad4 NFE exome AF: 0.0302

Gnomad4 OTH exome AF: 0.0462

GnomAD4 genome AF: 0.0604 AC: 9196 AN: 152196 Hom.: 353 Cov.: 32 AF XY: 0.0618 AC XY: 4601 AN XY: 74404

Gnomad4 AFR AF: 0.0899

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0616

Gnomad4 FIN AF: 0.0289

Gnomad4 NFE AF: 0.0355

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0486 Hom.: 50

Bravo AF: 0.0662

Asia WGS AF: 0.0960 AC: 331 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	0.45
DANN	Benign	0.68

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: rs3918400; hg19: chr20-3649463;