rs3752661

Variant names:

• chr2-10443896-T-C
• rs3752661
• NM_002539.3:c.450-60A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-10443896-T-C
• chr2-10443896-T-G

Variant summary

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

The NM_002539.3(ODC1):​c.450-60A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 1,595,056 control chromosomes in the GnomAD database, including 9,143 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 (1471 hom., cov: 33)
  • Exomes 𝑓: 0.062 (7672 hom.)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODC1	NM_002539.3	c.450-60A>G		intron_variant	Intron 5 of 11	ENST00000234111.9	NP_002530.1
ODC1	NM_001287189.2	c.450-60A>G		intron_variant	Intron 5 of 11		NP_001274118.1
ODC1	NM_001287190.2	c.450-60A>G		intron_variant	Intron 5 of 11		NP_001274119.1
ODC1	NM_001287188.2	c.63-60A>G		intron_variant	Intron 5 of 11		NP_001274117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODC1	ENST00000234111.9	c.450-60A>G		intron_variant	Intron 5 of 11	1	NM_002539.3	ENSP00000234111.4

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15647 AN: 152036 Hom.: 1470 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0384

Gnomad OTH AF: 0.0852

GnomAD4 exome AF: 0.0617 AC: 89085 AN: 1442902 Hom.: 7672 Cov.: 30 AF XY: 0.0616 AC XY: 44046 AN XY: 715034

African (AFR) AF: 0.166 AC: 5440 AN: 32816

American (AMR) AF: 0.104 AC: 4516 AN: 43336

Ashkenazi Jewish (ASJ) AF: 0.0431 AC: 1115 AN: 25848

East Asian (EAS) AF: 0.505 AC: 19848 AN: 39274

South Asian (SAS) AF: 0.0861 AC: 7316 AN: 85002

European-Finnish (FIN) AF: 0.112 AC: 5967 AN: 53170

Middle Eastern (MID) AF: 0.0573 AC: 326 AN: 5688

European-Non Finnish (NFE) AF: 0.0362 AC: 39767 AN: 1098176

Other (OTH) AF: 0.0804 AC: 4790 AN: 59592

GnomAD4 genome AF: 0.103 AC: 15657 AN: 152154 Hom.: 1471 Cov.: 33 AF XY: 0.109 AC XY: 8079 AN XY: 74400

African (AFR) AF: 0.166 AC: 6887 AN: 41478

American (AMR) AF: 0.0985 AC: 1507 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 149 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2548 AN: 5166

South Asian (SAS) AF: 0.0983 AC: 474 AN: 4822

European-Finnish (FIN) AF: 0.121 AC: 1279 AN: 10590

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0384 AC: 2612 AN: 68008

Other (OTH) AF: 0.0833 AC: 176 AN: 2112

Alfa AF: 0.0916 Hom.: 427

Bravo AF: 0.106

Asia WGS AF: 0.269 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.91
DANN	Benign	0.48
PhyloP100		-0.92
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: rs3752661; hg19: chr2-10584022; COSMIC: COSV52172881; COSMIC: COSV52172881;