rs28362416

Variant names:

• chr2-10441143-G-A
• rs28362416
• NM_002539.3:c.1242-275C>T

Variant summary

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

The NM_002539.3(ODC1):​c.1242-275C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 152,136 control chromosomes in the GnomAD database, including 254 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 0.047 (254 hom., cov: 32)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 2 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]

ODC1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with alopecia and brain abnormalities

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000298698 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.067 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODC1	NM_002539.3	c.1242-275C>T		intron_variant	Intron 11 of 11	ENST00000234111.9	NP_002530.1
ODC1	NM_001287189.2	c.1242-275C>T		intron_variant	Intron 11 of 11		NP_001274118.1
ODC1	NM_001287190.2	c.1242-275C>T		intron_variant	Intron 11 of 11		NP_001274119.1
ODC1	NM_001287188.2	c.855-275C>T		intron_variant	Intron 11 of 11		NP_001274117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.1242-275C>T		intron_variant	Intron 11 of 11	1	NM_002539.3	ENSP00000234111.4

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 7222 AN: 152018 Hom.: 255 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0474 AC: 7218 AN: 152136 Hom.: 254 Cov.: 32 AF XY: 0.0467 AC XY: 3476 AN XY: 74380

African (AFR) AF: 0.0136 AC: 564 AN: 41500

American (AMR) AF: 0.0487 AC: 744 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0156 AC: 75 AN: 4818

European-Finnish (FIN) AF: 0.0784 AC: 829 AN: 10572

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0686 AC: 4668 AN: 68002

Other (OTH) AF: 0.0492 AC: 104 AN: 2112

Alfa AF: 0.0526 Hom.: 30

Bravo AF: 0.0441

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.1
DANN	Benign	0.85
PhyloP100		2.0
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: rs28362416; hg19: chr2-10581269;