15-73126400-ATTTT-ATTTTTTT
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_002499.4(NEO1):c.725-5_725-3dupTTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000942 in 1,167,814 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000094 ( 0 hom. )
Consequence
NEO1
NM_002499.4 splice_acceptor, intron
NM_002499.4 splice_acceptor, intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.242
Publications
0 publications found
Genes affected
NEO1 (HGNC:7754): (neogenin 1) This gene encodes a cell surface protein that is a member of the immunoglobulin superfamily. The encoded protein consists of four N-terminal immunoglobulin-like domains, six fibronectin type III domains, a transmembrane domain and a C-terminal internal domain that shares homology with the tumor suppressor candidate gene DCC. This protein may be involved in cell growth and differentiation and in cell-cell adhesion. Defects in this gene are associated with cell proliferation in certain cancers. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.035111718 fraction of the gene. Cryptic splice site detected, with MaxEntScore 12, offset of 0 (no position change), new splice context is: atttttttttttttttttAGatc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002499.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| NEO1 | NM_002499.4 | MANE Select | c.725-5_725-3dupTTT | splice_acceptor intron | N/A | NP_002490.2 | Q92859-1 | ||
| NEO1 | NM_001419531.1 | c.725-5_725-3dupTTT | splice_acceptor intron | N/A | NP_001406460.1 | ||||
| NEO1 | NM_001172624.2 | c.725-5_725-3dupTTT | splice_acceptor intron | N/A | NP_001166095.1 | Q92859-4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NEO1 | ENST00000261908.11 | TSL:1 MANE Select | c.725-17_725-16insTTT | intron | N/A | ENSP00000261908.6 | Q92859-1 | ||
| NEO1 | ENST00000558964.5 | TSL:1 | c.725-17_725-16insTTT | intron | N/A | ENSP00000453200.1 | Q92859-4 | ||
| NEO1 | ENST00000560262.5 | TSL:1 | c.725-17_725-16insTTT | intron | N/A | ENSP00000453317.1 | Q92859-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000942 AC: 11AN: 1167814Hom.: 0 Cov.: 0 AF XY: 0.0000103 AC XY: 6AN XY: 582428 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
11
AN:
1167814
Hom.:
Cov.:
0
AF XY:
AC XY:
6
AN XY:
582428
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
25778
American (AMR)
AF:
AC:
0
AN:
31008
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
21264
East Asian (EAS)
AF:
AC:
1
AN:
34442
South Asian (SAS)
AF:
AC:
2
AN:
66382
European-Finnish (FIN)
AF:
AC:
0
AN:
40232
Middle Eastern (MID)
AF:
AC:
0
AN:
4734
European-Non Finnish (NFE)
AF:
AC:
6
AN:
894926
Other (OTH)
AF:
AC:
0
AN:
49048
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.261
Heterozygous variant carriers
0
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4
6
7
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0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
BranchPoint Hunter
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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