NM_002539.3:c.-127-1390A>G

Variant names:

• chr2-10446654-T-C
• rs28362380
• NM_002539.3:c.-127-1390A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002539.3(ODC1):​c.-127-1390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 307,362 control chromosomes in the GnomAD database, including 1,796 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 0.091 (806 hom., cov: 33)
  • Exomes 𝑓: 0.10 (990 hom.)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• 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]

SNORA80B (HGNC:34355): (small nucleolar RNA, H/ACA box 80B)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002539.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	NM_002539.3	MANE Select	c.-127-1390A>G		intron	N/A	NP_002530.1
	ODC1	NM_001287189.2		c.-128+820A>G		intron	N/A	NP_001274118.1
	ODC1	NM_001287190.2		c.-128+974A>G		intron	N/A	NP_001274119.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	ENST00000234111.9	TSL:1 MANE Select	c.-127-1390A>G		intron	N/A	ENSP00000234111.4
	ODC1	ENST00000405333.5	TSL:2	c.-128+820A>G		intron	N/A	ENSP00000385333.1
	ODC1	ENST00000443218.2	TSL:2	c.-128+974A>G		intron	N/A	ENSP00000390691.2

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13864 AN: 152174 Hom.: 806 Cov.: 33

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.0899

GnomAD4 exome AF: 0.0999 AC: 15489 AN: 155070 Hom.: 990 AF XY: 0.0993 AC XY: 9300 AN XY: 93674

African (AFR) AF: 0.0421 AC: 62 AN: 1472

American (AMR) AF: 0.217 AC: 1103 AN: 5090

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 348 AN: 3684

East Asian (EAS) AF: 0.221 AC: 448 AN: 2026

South Asian (SAS) AF: 0.104 AC: 3621 AN: 34756

European-Finnish (FIN) AF: 0.0956 AC: 695 AN: 7268

Middle Eastern (MID) AF: 0.0370 AC: 31 AN: 838

European-Non Finnish (NFE) AF: 0.0916 AC: 8492 AN: 92678

Other (OTH) AF: 0.0949 AC: 689 AN: 7258

GnomAD4 genome AF: 0.0911 AC: 13872 AN: 152292 Hom.: 806 Cov.: 33 AF XY: 0.0939 AC XY: 6988 AN XY: 74450

African (AFR) AF: 0.0456 AC: 1896 AN: 41576

American (AMR) AF: 0.175 AC: 2673 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 298 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1072 AN: 5180

South Asian (SAS) AF: 0.101 AC: 489 AN: 4830

European-Finnish (FIN) AF: 0.0880 AC: 934 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0915 AC: 6227 AN: 68022

Other (OTH) AF: 0.0913 AC: 193 AN: 2114

Alfa AF: 0.0861 Hom.: 106

Bravo AF: 0.0995

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs28362380; hg19: chr2-10586780;