20-49070216-A-G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001316.4(CSE1L):c.687A>G(p.Glu229Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,436,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Consequence
CSE1L
NM_001316.4 synonymous
NM_001316.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.462
Publications
0 publications found
Genes affected
CSE1L (HGNC:2431): (chromosome segregation 1 like) Proteins that carry a nuclear localization signal (NLS) are transported into the nucleus by the importin-alpha/beta heterodimer. Importin-alpha binds the NLS, while importin-beta mediates translocation through the nuclear pore complex. After translocation, RanGTP binds importin-beta and displaces importin-alpha. Importin-alpha must then be returned to the cytoplasm, leaving the NLS protein behind. The protein encoded by this gene binds strongly to NLS-free importin-alpha, and this binding is released in the cytoplasm by the combined action of RANBP1 and RANGAP1. In addition, the encoded protein may play a role both in apoptosis and in cell proliferation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP7
Synonymous conserved (PhyloP=0.462 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001316.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| CSE1L | MANE Select | c.687A>G | p.Glu229Glu | synonymous | Exon 8 of 25 | NP_001307.2 | |||
| CSE1L | c.687A>G | p.Glu229Glu | synonymous | Exon 8 of 25 | NP_001349691.1 | P55060-3 | |||
| CSE1L | c.687A>G | p.Glu229Glu | synonymous | Exon 8 of 24 | NP_001243064.1 | P55060-4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CSE1L | TSL:1 MANE Select | c.687A>G | p.Glu229Glu | synonymous | Exon 8 of 25 | ENSP00000262982.2 | P55060-1 | ||
| CSE1L | c.687A>G | p.Glu229Glu | synonymous | Exon 9 of 26 | ENSP00000559123.1 | ||||
| CSE1L | c.687A>G | p.Glu229Glu | synonymous | Exon 8 of 25 | ENSP00000603091.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152192
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000234 AC: 3AN: 1284434Hom.: 0 Cov.: 20 AF XY: 0.00000310 AC XY: 2AN XY: 644732 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1284434
Hom.:
Cov.:
20
AF XY:
AC XY:
2
AN XY:
644732
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
28456
American (AMR)
AF:
AC:
0
AN:
34438
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24066
East Asian (EAS)
AF:
AC:
0
AN:
37654
South Asian (SAS)
AF:
AC:
0
AN:
73824
European-Finnish (FIN)
AF:
AC:
0
AN:
52754
Middle Eastern (MID)
AF:
AC:
0
AN:
5396
European-Non Finnish (NFE)
AF:
AC:
3
AN:
973694
Other (OTH)
AF:
AC:
0
AN:
54152
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000625500), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.342
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
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
45-50
50-55
55-60
60-65
65-70
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74356 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152192
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74356
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41456
American (AMR)
AF:
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5200
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68016
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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