Genetic Variant ODC1:c.751-490A>G (chr2-10442664-T-C) – 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.751-490A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,182 control chromosomes in the GnomAD database, including 957 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 0.10 ( 957 hom., cov: 32)

Consequence

ODC1
NM_002539.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

4 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:

ENSG00000298698 (HGNC:):

ENSG00000298698 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ODC1	NM_002539.3 link	c.751-490A>G	intron_variant	Intron 8 of 11	ENST00000234111.9	NP_002530.1	P11926
ODC1	NM_001287189.2 link	c.751-490A>G	intron_variant	Intron 8 of 11		NP_001274118.1	P11926
ODC1	NM_001287190.2 link	c.751-490A>G	intron_variant	Intron 8 of 11		NP_001274119.1	P11926
ODC1	NM_001287188.2 link	c.364-490A>G	intron_variant	Intron 8 of 11		NP_001274117.1	B4DXF8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9 link	c.751-490A>G		intron_variant	Intron 8 of 11	1	NM_002539.3	ENSP00000234111.4		P11926

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15908

AN:

152074

Hom.:

957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0926

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.0818

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0883

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0919

Gnomad OTH

AF:

0.102

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

GnomAD4 genome

AF:

0.105

AC:

15919

AN:

152182

Hom.:

957

Cov.:

AF XY:

0.106

AC XY:

7911

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0925

AC:

3839

AN:

41518

American (AMR)

AF:

0.179

AC:

2732

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0818

AC:

284

AN:

3470

East Asian (EAS)

AF:

0.208

AC:

1077

AN:

5176

South Asian (SAS)

AF:

0.102

AC:

493

AN:

4820

European-Finnish (FIN)

AF:

0.0883

AC:

935

AN:

10584

Middle Eastern (MID)

AF:

0.0342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0919

AC:

6251

AN:

68004

Other (OTH)

AF:

0.103

AC:

218

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

716

1432

2147

2863

3579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.105

Hom.:

378

Bravo

AF:

0.114

Asia WGS

AF:

0.173

AC:

601

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.24

(source)

DANN

Benign

0.73

PhyloP100

-1.4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over