2-10447043-T-A

Position:

• chr2-10447043-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002539.3(ODC1):​c.-128+1078A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,252 control chromosomes in the GnomAD database, including 2,506 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 0.16 (2506 hom., cov: 33)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODC1	NM_002539.3	c.-128+1078A>T		intron_variant		ENST00000234111.9
ODC1	NM_001287188.2	c.-415+1078A>T		intron_variant
ODC1	NM_001287189.2	c.-128+431A>T		intron_variant
ODC1	NM_001287190.2	c.-128+585A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODC1	ENST00000234111.9	c.-128+1078A>T		intron_variant		1	NM_002539.3	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24108 AN: 152132 Hom.: 2493 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.159 AC: 24165 AN: 152252 Hom.: 2506 Cov.: 33 AF XY: 0.160 AC XY: 11895 AN XY: 74446

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.0859

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.0925

Gnomad4 OTH AF: 0.128

Alfa AF: 0.127 Hom.: 205

Bravo AF: 0.176

Asia WGS AF: 0.187 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.33

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

LitVar

Other links and lift over

dbSNP: rs7558559; hg19: chr2-10587169;