20-33676727-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005225.3(E2F1):​c.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,100 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: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

E2F1
NM_005225.3 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.881

Publications

0 publications found
Variant links:
Genes affected
E2F1 (HGNC:3113): (E2F transcription factor 1) 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 and another 2 members, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
E2F1NM_005225.3 linkc.*5G>A 3_prime_UTR_variant Exon 7 of 7 ENST00000343380.6 NP_005216.1 Q01094Q9BSD8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
E2F1ENST00000343380.6 linkc.*5G>A 3_prime_UTR_variant Exon 7 of 7 1 NM_005225.3 ENSP00000345571.5 Q01094

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1453100
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
722156
show subpopulations
African (AFR)
AF:
0.0000300
AC:
1
AN:
33354
American (AMR)
AF:
0.00
AC:
0
AN:
43846
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25612
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39520
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84778
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52240
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5718
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1107978
Other (OTH)
AF:
0.00
AC:
0
AN:
60054
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
11
DANN
Benign
0.89
PhyloP100
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs3213177; hg19: chr20-32264533; API