rs1028853905

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004424.5(E4F1):​c.326C>G​(p.Pro109Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P109L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

E4F1
NM_004424.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.836
Variant links:
Genes affected
E4F1 (HGNC:3121): (E4F transcription factor 1) The zinc finger protein encoded by this gene is one of several cellular transcription factors whose DNA-binding activities are regulated through the action of adenovirus E1A. A 50-kDa amino-terminal product is generated from the full-length protein through proteolytic cleavage. The protein is differentially regulated by E1A-induced phosphorylation. The full-length gene product represses transcription from the E4 promoter in the absence of E1A, while the 50-kDa form acts as a transcriptional activator in its presence. Alternative splicing results in multiple transcripts encoding different proteins. [provided by RefSeq, Jan 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.100503296).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
E4F1NM_004424.5 linkc.326C>G p.Pro109Arg missense_variant Exon 3 of 14 ENST00000301727.9 NP_004415.4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
E4F1ENST00000301727.9 linkc.326C>G p.Pro109Arg missense_variant Exon 3 of 14 1 NM_004424.5 ENSP00000301727.4 Q66K89

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459362
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726082
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
13
DANN
Benign
0.59
DEOGEN2
Benign
0.073
T;.;.;T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.78
T;T;T;T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.69
N;.;.;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.42
N;N;N;N
REVEL
Benign
0.043
Sift
Uncertain
0.0080
D;T;D;T
Sift4G
Benign
0.45
T;T;T;T
Polyphen
0.0
B;.;.;.
Vest4
0.24
MutPred
0.32
Loss of glycosylation at P109 (P = 0.0261);Loss of glycosylation at P109 (P = 0.0261);Loss of glycosylation at P109 (P = 0.0261);.;
MVP
0.50
MPC
0.41
ClinPred
0.23
T
GERP RS
4.4
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.079
gMVP
0.15

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2279587; API