rs3918395

Positions:

• chr20-3672502-C-A
• chr20-3672502-C-T

Variant summary

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

The NM_025220.5(ADAM33):​c.1401+35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,603,666 control chromosomes in the GnomAD database, including 13,902 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 0.13 (1303 hom., cov: 34)
  • Exomes 𝑓: 0.13 (12599 hom.)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.1401+35G>T		intron_variant		ENST00000356518.7	NP_079496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM33	ENST00000356518.7	c.1401+35G>T		intron_variant		1	NM_025220.5	ENSP00000348912.3
ADAM33	ENST00000379861.8	c.1401+35G>T		intron_variant		1		ENSP00000369190.4
ADAM33	ENST00000466620.5	n.1040+35G>T		intron_variant		1
ADAM33	ENST00000350009.6	c.1401+35G>T		intron_variant		5		ENSP00000322550.5

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19899 AN: 152140 Hom.: 1302 Cov.: 34

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.140

GnomAD3 exomes AF: 0.129 AC: 30868 AN: 239596 Hom.: 2169 AF XY: 0.134 AC XY: 17475 AN XY: 130328

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.0659

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0848

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.129 AC: 187561 AN: 1451408 Hom.: 12599 Cov.: 36 AF XY: 0.132 AC XY: 94723 AN XY: 720214

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.0690

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.131 AC: 19898 AN: 152258 Hom.: 1303 Cov.: 34 AF XY: 0.132 AC XY: 9846 AN XY: 74442

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0959

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.138

Alfa AF: 0.130 Hom.: 1848

Bravo AF: 0.121

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.0
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3918395; hg19: chr20-3653149;