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Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BA1
The NM_001950.4(E2F4):c.950_958dupGCAGCAGCA(p.Ser317_Ser319dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 1,607,948 control chromosomes in the GnomAD database, including 106 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.019 ( 100 hom., cov: 31)
Exomes 𝑓: 0.0032 ( 6 hom. )
Consequence
E2F4
NM_001950.4 disruptive_inframe_insertion
NM_001950.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.01
Publications
11 publications found
Genes affected
E2F4 (HGNC:3118): (E2F transcription factor 4) The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein binds to all three of the tumor suppressor proteins pRB, p107 and p130, but with higher affinity to the last two. It plays an important role in the suppression of proliferation-associated genes, and its gene mutation and increased expression may be associated with human cancer. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -9 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_001950.4
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001950.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| E2F4 | NM_001950.4 | MANE Select | c.950_958dupGCAGCAGCA | p.Ser317_Ser319dup | disruptive_inframe_insertion | Exon 7 of 10 | NP_001941.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| E2F4 | ENST00000379378.8 | TSL:1 MANE Select | c.950_958dupGCAGCAGCA | p.Ser317_Ser319dup | disruptive_inframe_insertion | Exon 7 of 10 | ENSP00000368686.3 | Q16254 | |
| E2F4 | ENST00000914909.1 | c.950_958dupGCAGCAGCA | p.Ser317_Ser319dup | disruptive_inframe_insertion | Exon 7 of 10 | ENSP00000584968.1 | |||
| E2F4 | ENST00000957228.1 | c.965_973dupGCAGCAGCA | p.Ser322_Ser324dup | disruptive_inframe_insertion | Exon 7 of 10 | ENSP00000627287.1 |
Frequencies
GnomAD3 genomes 0.0191 AC: 2875AN: 150322Hom.: 99 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
2875
AN:
150322
Hom.:
Cov.:
31
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: 0.00315 AC: 4595AN: 1457530Hom.: 6 Cov.: 30 AF XY: 0.00300 AC XY: 2176AN XY: 724980 show subpopulations
GnomAD4 exome
AF:
AC:
4595
AN:
1457530
Hom.:
Cov.:
30
AF XY:
AC XY:
2176
AN XY:
724980
show subpopulations
African (AFR)
AF:
AC:
2088
AN:
32810
American (AMR)
AF:
AC:
292
AN:
44572
Ashkenazi Jewish (ASJ)
AF:
AC:
86
AN:
26076
East Asian (EAS)
AF:
AC:
358
AN:
39534
South Asian (SAS)
AF:
AC:
286
AN:
85728
European-Finnish (FIN)
AF:
AC:
7
AN:
53052
Middle Eastern (MID)
AF:
AC:
56
AN:
5728
European-Non Finnish (NFE)
AF:
AC:
1068
AN:
1109934
Other (OTH)
AF:
AC:
354
AN:
60096
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.429
Heterozygous variant carriers
0
274
548
822
1096
1370
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
96
192
288
384
480
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0192 AC: 2888AN: 150418Hom.: 100 Cov.: 31 AF XY: 0.0187 AC XY: 1370AN XY: 73430 show subpopulations
GnomAD4 genome
AF:
AC:
2888
AN:
150418
Hom.:
Cov.:
31
AF XY:
AC XY:
1370
AN XY:
73430
show subpopulations
African (AFR)
AF:
AC:
2494
AN:
40810
American (AMR)
AF:
AC:
175
AN:
15116
Ashkenazi Jewish (ASJ)
AF:
AC:
13
AN:
3464
East Asian (EAS)
AF:
AC:
65
AN:
5132
South Asian (SAS)
AF:
AC:
20
AN:
4772
European-Finnish (FIN)
AF:
AC:
3
AN:
10260
Middle Eastern (MID)
AF:
AC:
3
AN:
294
European-Non Finnish (NFE)
AF:
AC:
84
AN:
67572
Other (OTH)
AF:
AC:
31
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
118
237
355
474
592
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
30
60
90
120
150
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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