rs28742580

Variant names:

• chr2-10448426-C-A
• rs28742580
• NM_002539.3:c.-433G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-10448426-C-A
• chr2-10448426-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002539.3(ODC1):​c.-433G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 92,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: ODC1 NM_002539.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 6 publications found

Genes affected

ODC1 (HGNC:8109): (ornithine decarboxylase 1) This gene encodes the rate-limiting enzyme of the polyamine biosynthesis pathway which catalyzes ornithine to putrescine. The activity level for the enzyme varies in response to growth-promoting stimuli and exhibits a high turnover rate in comparison to other mammalian proteins. Originally localized to both chromosomes 2 and 7, the gene encoding this enzyme has been determined to be located on 2p25, with a pseudogene located on 7q31-qter. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Dec 2013]

ODC1-DT (HGNC:54070): (ODC1 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODC1	NM_002539.3	c.-433G>T		upstream_gene_variant		ENST00000234111.9	NP_002530.1
ODC1	NM_001287188.2	c.-720G>T		upstream_gene_variant			NP_001274117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.-433G>T		upstream_gene_variant		1	NM_002539.3	ENSP00000234111.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000215 AC: 2 AN: 92816 Hom.: 0 Cov.: 0 AF XY: 0.0000406 AC XY: 2 AN XY: 49238

African (AFR) AF: 0.00 AC: 0 AN: 1856

American (AMR) AF: 0.00 AC: 0 AN: 2728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2892

East Asian (EAS) AF: 0.00 AC: 0 AN: 8758

South Asian (SAS) AF: 0.000619 AC: 1 AN: 1616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 476

European-Non Finnish (NFE) AF: 0.0000166 AC: 1 AN: 60304

Other (OTH) AF: 0.00 AC: 0 AN: 5392

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		0.11
PromoterAI		0.034	Neutral

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

Other links and lift over

dbSNP: rs28742580; hg19: chr2-10588552;