rs7608353

Variant names:

• chr2-10446664-A-G
• rs7608353
• NM_002539.3:c.-127-1400T>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.-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
• 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]

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

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 (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002539.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	NM_002539.3	MANE Select	c.-127-1400T>C		intron	N/A	NP_002530.1	P11926
	ODC1	NM_001287189.2		c.-128+810T>C		intron	N/A	NP_001274118.1	P11926
	ODC1	NM_001287190.2		c.-128+964T>C		intron	N/A	NP_001274119.1	P11926

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODC1	ENST00000234111.9	TSL:1 MANE Select	c.-127-1400T>C		intron	N/A	ENSP00000234111.4	P11926
	ODC1	ENST00000926729.1		c.-582T>C		5_prime_UTR	Exon 1 of 12	ENSP00000596788.1
	ODC1	ENST00000405333.5	TSL:2	c.-128+810T>C		intron	N/A	ENSP00000385333.1	P11926

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

African (AFR) AF: 0.0861 AC: 146 AN: 1696

American (AMR) AF: 0.239 AC: 1538 AN: 6448

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 428 AN: 4562

East Asian (EAS) AF: 0.228 AC: 605 AN: 2650

South Asian (SAS) AF: 0.105 AC: 4128 AN: 39178

European-Finnish (FIN) AF: 0.0963 AC: 825 AN: 8568

Middle Eastern (MID) AF: 0.0453 AC: 53 AN: 1170

European-Non Finnish (NFE) AF: 0.0940 AC: 9944 AN: 105750

Other (OTH) AF: 0.0995 AC: 823 AN: 8268

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

African (AFR) AF: 0.0840 AC: 3488 AN: 41530

American (AMR) AF: 0.184 AC: 2809 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 298 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1072 AN: 5180

South Asian (SAS) AF: 0.101 AC: 489 AN: 4832

European-Finnish (FIN) AF: 0.0880 AC: 933 AN: 10600

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0918 AC: 6241 AN: 67998

Other (OTH) AF: 0.0990 AC: 209 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.57
PhyloP100		0.58
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: rs7608353; hg19: chr2-10586790; COSMIC: COSV52172320; COSMIC: COSV52172320;