rs1405948

Variant names:

• chr2-10443034-G-A
• rs1405948
• NM_002539.3:c.750+196C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-10443034-G-A
• chr2-10443034-G-C
• chr2-10443034-G-T

Variant summary

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

The NM_002539.3(ODC1):​c.750+196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,106 control chromosomes in the GnomAD database, including 927 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 (927 hom., cov: 32)
• Consequence: ODC1 NM_002539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 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.750+196C>T		intron	N/A	NP_002530.1	P11926
	ODC1	NM_001287189.2		c.750+196C>T		intron	N/A	NP_001274118.1	P11926
	ODC1	NM_001287190.2		c.750+196C>T		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.750+196C>T		intron	N/A	ENSP00000234111.4	P11926
	ODC1	ENST00000405333.5	TSL:2	c.750+196C>T		intron	N/A	ENSP00000385333.1	P11926
	ODC1	ENST00000443218.2	TSL:2	c.750+196C>T		intron	N/A	ENSP00000390691.2	P11926

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15363 AN: 151986 Hom.: 927 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.0961

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

GnomAD4 genome AF: 0.101 AC: 15386 AN: 152106 Hom.: 927 Cov.: 32 AF XY: 0.104 AC XY: 7731 AN XY: 74360

African (AFR) AF: 0.0835 AC: 3464 AN: 41468

American (AMR) AF: 0.184 AC: 2812 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1067 AN: 5174

South Asian (SAS) AF: 0.100 AC: 484 AN: 4822

European-Finnish (FIN) AF: 0.0880 AC: 931 AN: 10578

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

European-Non Finnish (NFE) AF: 0.0896 AC: 6093 AN: 67982

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.0958 Hom.: 3492

Bravo AF: 0.111

Asia WGS AF: 0.169 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		0.24
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: rs1405948; hg19: chr2-10583160;