rs2302616

Positions:

• chr2-10448065-C-A

Variant summary

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

The NM_002539.3(ODC1):​c.-128+56G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 158,658 control chromosomes in the GnomAD database, including 6,082 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 0.26 (5726 hom., cov: 35)
  • Exomes 𝑓: 0.31 (356 hom.)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODC1	NM_002539.3	c.-128+56G>T		intron_variant		ENST00000234111.9	NP_002530.1
ODC1	NM_001287188.2	c.-415+56G>T		intron_variant			NP_001274117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.-128+56G>T		intron_variant		1	NM_002539.3	ENSP00000234111	P1
ODC1	ENST00000699836.1	c.-18+56G>T		intron_variant				ENSP00000514634	P1
ODC1	ENST00000446285.6	c.-128+56G>T		intron_variant, NMD_transcript_variant		5		ENSP00000514632

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38783 AN: 151784 Hom.: 5727 Cov.: 35

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0676

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.308 AC: 2085 AN: 6768 Hom.: 356 AF XY: 0.308 AC XY: 1213 AN XY: 3938

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.255 AC: 38785 AN: 151890 Hom.: 5726 Cov.: 35 AF XY: 0.251 AC XY: 18606 AN XY: 74268

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0672

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.253

Alfa AF: 0.292 Hom.: 861

Bravo AF: 0.237

Asia WGS AF: 0.158 AC: 542 AN: 3416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.5
DANN	Benign	0.73
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		3.5

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: rs2302616; hg19: chr2-10588191;