dbSNP rs2302616: ODC1:c.-128+56G>T (chr2-10448065-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.465

Publications

9 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with alopecia and brain abnormalities
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ODC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
ODC1	NM_002539.3 link	c.-128+56G>T	intron_variant	Intron 1 of 11	ENST00000234111.9	NP_002530.1
ODC1	NM_001287188.2 link	c.-415+56G>T	intron_variant	Intron 1 of 11		NP_001274117.1
ODC1	NM_001287189.2 link	c.-719G>T	upstream_gene_variant			NP_001274118.1
ODC1	NM_001287190.2 link	c.-565G>T	upstream_gene_variant			NP_001274119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9 link	c.-128+56G>T		intron_variant	Intron 1 of 11	1	NM_002539.3	ENSP00000234111.4

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38783

AN:

151784

Hom.:

5727

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.169

AC:

AN:

130

American (AMR)

AF:

0.172

AC:

AN:

238

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

AN:

160

East Asian (EAS)

AF:

0.0625

AC:

AN:

224

South Asian (SAS)

AF:

0.188

AC:

AN:

European-Finnish (FIN)

AF:

0.335

AC:

287

AN:

856

Middle Eastern (MID)

AF:

0.261

AC:

AN:

European-Non Finnish (NFE)

AF:

0.332

AC:

1518

AN:

4578

Other (OTH)

AF:

0.285

AC:

130

AN:

456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

140

209

279

349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.255

AC:

38785

AN:

151890

Hom.:

5726

Cov.:

AF XY:

0.251

AC XY:

18606

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.132

AC:

5490

AN:

41490

American (AMR)

AF:

0.202

AC:

3086

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

970

AN:

3468

East Asian (EAS)

AF:

0.0672

AC:

347

AN:

5164

South Asian (SAS)

AF:

0.279

AC:

1350

AN:

4834

European-Finnish (FIN)

AF:

0.319

AC:

3354

AN:

10508

Middle Eastern (MID)

AF:

0.305

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.340

AC:

23093

AN:

67854

Other (OTH)

AF:

0.253

AC:

535

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1513

3027

4540

6054

7567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.73

PhyloP100

-0.47

PromoterAI

0.037

Neutral

(source)

RBP_binding_hub_radar

0.91

RBP_regulation_power_radar

3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over