chr20-3681193-C-G

Position:

• chr20-3681193-C-G

Variant summary

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

The NM_025220.5(ADAM33):​c.97+715G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,034 control chromosomes in the GnomAD database, including 12,621 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 0.40 (12621 hom., cov: 33)
• Consequence: ADAM33 NM_025220.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM33	NM_025220.5	c.97+715G>C		intron_variant		ENST00000356518.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM33	ENST00000356518.7	c.97+715G>C		intron_variant		1	NM_025220.5	P4
ADAM33	ENST00000379861.8	c.97+715G>C		intron_variant		1		A2
ADAM33	ENST00000350009.6	c.97+715G>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61232 AN: 151916 Hom.: 12586 Cov.: 33

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.403 AC: 61319 AN: 152034 Hom.: 12621 Cov.: 33 AF XY: 0.408 AC XY: 30299 AN XY: 74306

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.390

Alfa AF: 0.231 Hom.: 533

Bravo AF: 0.413

Asia WGS AF: 0.542 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.9
DANN	Benign	0.75

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: rs2853213; hg19: chr20-3661840;