rs7559979

Variant names:

• chr2-10442553-A-G
• rs7559979
• NM_002539.3:c.751-379T>C

Variant summary

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

The NM_002539.3(ODC1):​c.751-379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,006 control chromosomes in the GnomAD database, including 18,023 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 0.47 (18023 hom., cov: 32)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODC1	NM_002539.3	c.751-379T>C		intron_variant	Intron 8 of 11	ENST00000234111.9	NP_002530.1
ODC1	NM_001287189.2	c.751-379T>C		intron_variant	Intron 8 of 11		NP_001274118.1
ODC1	NM_001287190.2	c.751-379T>C		intron_variant	Intron 8 of 11		NP_001274119.1
ODC1	NM_001287188.2	c.364-379T>C		intron_variant	Intron 8 of 11		NP_001274117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.751-379T>C		intron_variant	Intron 8 of 11	1	NM_002539.3	ENSP00000234111.4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70671 AN: 151888 Hom.: 17989 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.466 AC: 70769 AN: 152006 Hom.: 18023 Cov.: 32 AF XY: 0.477 AC XY: 35443 AN XY: 74288

African (AFR) AF: 0.639 AC: 26506 AN: 41456

American (AMR) AF: 0.463 AC: 7068 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3468

East Asian (EAS) AF: 0.774 AC: 4007 AN: 5176

South Asian (SAS) AF: 0.520 AC: 2504 AN: 4818

European-Finnish (FIN) AF: 0.487 AC: 5133 AN: 10540

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23372 AN: 67966

Other (OTH) AF: 0.421 AC: 884 AN: 2102

Alfa AF: 0.383 Hom.: 18218

Bravo AF: 0.476

Asia WGS AF: 0.657 AC: 2282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.14
DANN	Benign	0.59
PhyloP100		-2.4
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: rs7559979; hg19: chr2-10582679;