rs7608353

Positions:

• chr2-10446664-A-G

Variant summary

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

The NM_002539.3(ODC1):​c.-127-1400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 330,504 control chromosomes in the GnomAD database, including 2,100 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 (936 hom., cov: 33)
  • Exomes 𝑓: 0.10 (1164 hom.)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579

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]

SNORA80B (HGNC:34355): (small nucleolar RNA, H/ACA box 80B)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODC1	NM_002539.3	c.-127-1400T>C		intron_variant		ENST00000234111.9
SNORA80B	NR_028374.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODC1	ENST00000234111.9	c.-127-1400T>C		intron_variant		1	NM_002539.3	P1
SNORA80B	ENST00000383906.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15606 AN: 152096 Hom.: 936 Cov.: 33

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0918

Gnomad OTH AF: 0.0976

GnomAD4 exome AF: 0.104 AC: 18490 AN: 178290 Hom.: 1164 Cov.: 0 AF XY: 0.102 AC XY: 11014 AN XY: 107636

Gnomad4 AFR exome AF: 0.0861

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.0938

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0963

Gnomad4 NFE exome AF: 0.0940

Gnomad4 OTH exome AF: 0.0995

GnomAD4 genome AF: 0.103 AC: 15629 AN: 152214 Hom.: 936 Cov.: 33 AF XY: 0.105 AC XY: 7836 AN XY: 74420

Gnomad4 AFR AF: 0.0840

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.0858

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0880

Gnomad4 NFE AF: 0.0918

Gnomad4 OTH AF: 0.0990

Alfa AF: 0.0941 Hom.: 119

Bravo AF: 0.113

Asia WGS AF: 0.172 AC: 598 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	9.9
DANN	Benign	0.57

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: rs7608353; hg19: chr2-10586790; COSMIC: COSV52172320; COSMIC: COSV52172320;