rs1764996

Variant names:

• chr20-4142158-C-T
• rs1764996
• ENST00000493223.1:n.205+20974C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000493223.1(SMOX):​n.205+20974C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 152,210 control chromosomes in the GnomAD database, including 770 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 0.086 (770 hom., cov: 32)
• Consequence: SMOX ENST00000493223.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 2 publications found

Genes affected

SMOX (HGNC:15862): (spermine oxidase) Polyamines are ubiquitous polycationic alkylamines which include spermine, spermidine, putrescine, and agmatine. These molecules participate in a broad range of cellular functions which include cell cycle modulation, scavenging reactive oxygen species, and the control of gene expression. These molecules also play important roles in neurotransmission through their regulation of cell-surface receptor activity, involvement in intracellular signalling pathways, and their putative roles as neurotransmitters. This gene encodes an FAD-containing enzyme that catalyzes the oxidation of spermine to spermadine and secondarily produces hydrogen peroxide. Multiple transcript variants encoding different isoenzymes have been identified for this gene, some of which have failed to demonstrate significant oxidase activity on natural polyamine substrates. The characterized isoenzymes have distinctive biochemical characteristics and substrate specificities, suggesting the existence of additional levels of complexity in polyamine catabolism. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000493223.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOX	ENST00000493223.1	TSL:3	n.205+20974C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13064 AN: 152092 Hom.: 769 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0420

Gnomad OTH AF: 0.0934

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

GnomAD4 genome AF: 0.0859 AC: 13081 AN: 152210 Hom.: 770 Cov.: 32 AF XY: 0.0870 AC XY: 6474 AN XY: 74422

African (AFR) AF: 0.152 AC: 6311 AN: 41500

American (AMR) AF: 0.118 AC: 1798 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.0883 AC: 457 AN: 5174

South Asian (SAS) AF: 0.132 AC: 637 AN: 4826

European-Finnish (FIN) AF: 0.0523 AC: 555 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0420 AC: 2855 AN: 68026

Other (OTH) AF: 0.0919 AC: 194 AN: 2110

Alfa AF: 0.0836 Hom.: 130

Bravo AF: 0.0937

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.43
PhyloP100		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1764996; hg19: chr20-4122805;