rs2302614

Positions:

• chr2-10445185-A-C
• chr2-10445185-A-G
• chr2-10445185-A-T

Variant summary

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

The NM_002539.3(ODC1):​c.-48T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 574,910 control chromosomes in the GnomAD database, including 8,751 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 0.13 (2310 hom., cov: 33)
  • Exomes 𝑓: 0.11 (6441 hom.)
• Consequence: ODC1 NM_002539.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODC1	NM_002539.3	c.-48T>G		5_prime_UTR_variant	2/12	ENST00000234111.9
ODC1	NM_001287188.2	c.-335T>G		5_prime_UTR_variant	2/12
ODC1	NM_001287189.2	c.-48T>G		5_prime_UTR_variant	2/12
ODC1	NM_001287190.2	c.-48T>G		5_prime_UTR_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODC1	ENST00000234111.9	c.-48T>G		5_prime_UTR_variant	2/12	1	NM_002539.3	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19789 AN: 152144 Hom.: 2306 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.111 AC: 46737 AN: 422648 Hom.: 6441 Cov.: 4 AF XY: 0.114 AC XY: 25566 AN XY: 224534

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.0492

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.0416

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.130 AC: 19821 AN: 152262 Hom.: 2310 Cov.: 33 AF XY: 0.138 AC XY: 10283 AN XY: 74454

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0394

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0461 Hom.: 92

Bravo AF: 0.135

Asia WGS AF: 0.360 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2302614; hg19: chr2-10585311;