rs12616336

Positions:

• chr2-10446534-A-G

Variant summary

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

The NM_002539.3(ODC1):​c.-127-1270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 152,322 control chromosomes in the GnomAD database, including 429 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 0.067 (429 hom., cov: 33)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODC1	NM_002539.3	c.-127-1270T>C		intron_variant		ENST00000234111.9	NP_002530.1
ODC1	NM_001287188.2	c.-414-1270T>C		intron_variant			NP_001274117.1
ODC1	NM_001287189.2	c.-128+940T>C		intron_variant			NP_001274118.1
ODC1	NM_001287190.2	c.-128+1094T>C		intron_variant			NP_001274119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.-127-1270T>C		intron_variant		1	NM_002539.3	ENSP00000234111	P1

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10171 AN: 152204 Hom.: 429 Cov.: 33

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.0442

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0668 AC: 10169 AN: 152322 Hom.: 429 Cov.: 33 AF XY: 0.0674 AC XY: 5016 AN XY: 74474

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0836

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.0441

Gnomad4 SAS AF: 0.0704

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.0908

Gnomad4 OTH AF: 0.0667

Alfa AF: 0.0820 Hom.: 114

Bravo AF: 0.0654

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12616336; hg19: chr2-10586660;