rs554743

Positions:

• chr20-3681495-C-T

Variant summary

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

The ENST00000356518.7(ADAM33):​c.97+413G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 151,958 control chromosomes in the GnomAD database, including 36,130 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 0.69 (36130 hom., cov: 31)
• Consequence: ADAM33 ENST00000356518.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM33	NM_025220.5	c.97+413G>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.97+413G>A		intron_variant		1	NM_025220.5	ENSP00000348912	P4
ADAM33	ENST00000379861.8	c.97+413G>A		intron_variant		1		ENSP00000369190	A2
ADAM33	ENST00000350009.6	c.97+413G>A		intron_variant		5		ENSP00000322550	A2

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104278 AN: 151840 Hom.: 36099 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.687 AC: 104362 AN: 151958 Hom.: 36130 Cov.: 31 AF XY: 0.690 AC XY: 51267 AN XY: 74274

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.720

Alfa AF: 0.703 Hom.: 30919

Bravo AF: 0.696

Asia WGS AF: 0.718 AC: 2496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.61

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: rs554743; hg19: chr20-3662142;