rs1764996

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOX	ENST00000493223.1	n.205+20974C>T		intron_variant	Intron 1 of 1	3

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

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.0883

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0523

Gnomad4 NFE AF: 0.0420

Gnomad4 OTH AF: 0.0919

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1764996; hg19: chr20-4122805;