Genetic Variant ODC1:c.-433G>C (chr2-10448426-C-G) – 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.-433G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 239,864 control chromosomes in the GnomAD database, including 46,629 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 0.65 ( 31624 hom., cov: 34)

Exomes 𝑓: 0.56 ( 15005 hom. )

Consequence

ODC1
NM_002539.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.112

Publications

6 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 links:

ODC1-DT (HGNC:54070): (ODC1 divergent transcript)

ODC1-DT links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODC1	NM_002539.3 link	c.-433G>C		upstream_gene_variant		ENST00000234111.9	NP_002530.1	P11926
ODC1	NM_001287188.2 link	c.-720G>C		upstream_gene_variant			NP_001274117.1	B4DXF8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9 link	c.-433G>C		upstream_gene_variant		1	NM_002539.3	ENSP00000234111.4		P11926

Frequencies

GnomAD3 genomes

AF:

0.645

AC:

95571

AN:

148118

Hom.:

31576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.705

Gnomad FIN

AF:

0.713

Gnomad MID

AF:

0.577

Gnomad NFE

AF:

0.601

Gnomad OTH

AF:

0.603

GnomAD4 exome

AF:

0.564

AC:

51646

AN:

91648

Hom.:

15005

Cov.:

AF XY:

0.562

AC XY:

27306

AN XY:

48610

show subpopulations

African (AFR)

AF:

0.706

AC:

1284

AN:

1818

American (AMR)

AF:

0.416

AC:

1121

AN:

2692

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1268

AN:

2854

East Asian (EAS)

AF:

0.571

AC:

4939

AN:

8646

South Asian (SAS)

AF:

0.677

AC:

1083

AN:

1600

European-Finnish (FIN)

AF:

0.639

AC:

5518

AN:

8638

Middle Eastern (MID)

AF:

0.530

AC:

250

AN:

472

European-Non Finnish (NFE)

AF:

0.558

AC:

33246

AN:

59614

Other (OTH)

AF:

0.553

AC:

2937

AN:

5314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

769

1538

2308

3077

3846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<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:

0.645

AC:

95668

AN:

148216

Hom.:

31624

Cov.:

AF XY:

0.649

AC XY:

46854

AN XY:

72218

show subpopulations

African (AFR)

AF:

0.764

AC:

31456

AN:

41164

American (AMR)

AF:

0.499

AC:

7466

AN:

14956

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1674

AN:

3396

East Asian (EAS)

AF:

0.633

AC:

3195

AN:

5048

South Asian (SAS)

AF:

0.704

AC:

3388

AN:

4812

European-Finnish (FIN)

AF:

0.713

AC:

6650

AN:

9332

Middle Eastern (MID)

AF:

0.579

AC:

168

AN:

290

European-Non Finnish (NFE)

AF:

0.601

AC:

39819

AN:

66248

Other (OTH)

AF:

0.605

AC:

1247

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1752

3505

5257

7010

8762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.635

Hom.:

3853

Bravo

AF:

0.632

Asia WGS

AF:

0.630

AC:

1863

AN:

2956

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

0.11

PromoterAI

0.064

Neutral

(source)

Mutation Taster

=300/0

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