Genetic Variant ENST00000757451.1:n.252-3787G>A (chr2-10439895-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000757451.1(ENSG00000298698):n.252-3787G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 152,582 control chromosomes in the GnomAD database, including 801 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 0.090 ( 801 hom., cov: 32)

Exomes 𝑓: 0.073 ( 0 hom. )

Consequence

ENSG00000298698
ENST00000757451.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.435

Publications

2 publications found

Variant links:

Genes affected

ENSG00000298698 (HGNC:):

ENSG00000298698 links:

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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000757451.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ODC1	NM_002539.3	MANE Select	c.*829C>T	downstream_gene	N/A	NP_002530.1	P11926
ODC1	NM_001287189.2		c.*829C>T	downstream_gene	N/A	NP_001274118.1	P11926
ODC1	NM_001287190.2		c.*829C>T	downstream_gene	N/A	NP_001274119.1	P11926

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000298698	ENST00000757451.1		n.252-3787G>A	intron	N/A
ENSG00000298698	ENST00000757452.1		n.133-1547G>A	intron	N/A
ODC1	ENST00000234111.9	TSL:1 MANE Select	c.*829C>T	downstream_gene	N/A	ENSP00000234111.4	P11926

Frequencies

GnomAD3 genomes

AF:

0.0897

AC:

13650

AN:

152106

Hom.:

801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.0808

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0876

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0900

Gnomad OTH

AF:

0.0864

GnomAD4 exome

AF:

0.0726

AC:

AN:

358

Hom.:

AF XY:

0.0720

AC XY:

AN XY:

250

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.100

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.0833

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0700

AC:

AN:

300

Other (OTH)

AF:

0.111

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0897

AC:

13657

AN:

152224

Hom.:

801

Cov.:

AF XY:

0.0926

AC XY:

6891

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0453

AC:

1883

AN:

41540

American (AMR)

AF:

0.175

AC:

2672

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0808

AC:

280

AN:

3466

East Asian (EAS)

AF:

0.204

AC:

1056

AN:

5176

South Asian (SAS)

AF:

0.101

AC:

486

AN:

4818

European-Finnish (FIN)

AF:

0.0876

AC:

929

AN:

10606

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0900

AC:

6120

AN:

68004

Other (OTH)

AF:

0.0879

AC:

186

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

643

1287

1930

2574

3217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<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:

0.0840

Hom.:

Bravo

AF:

0.0977

Asia WGS

AF:

0.167

AC:

579

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.4

(source)

DANN

Benign

0.79

PhyloP100

-0.43

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over