Genetic Variant E2F1:c.*5G>T (chr20-33676727-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005225.3(E2F1):c.*5G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,605,244 control chromosomes in the GnomAD database, including 2,014 homozygotes. 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 0.038 ( 160 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1854 hom. )

Consequence

E2F1
NM_005225.3 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.881

Publications

8 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]

E2F1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F1	NM_005225.3 link	c.*5G>T		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
E2F1	ENST00000343380.6 link	c.*5G>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_005225.3	ENSP00000345571.5		Q01094

Frequencies

GnomAD3 genomes

AF:

0.0375

AC:

5707

AN:

152138

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00893

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0790

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0375

Gnomad FIN

AF:

0.0481

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0459

Gnomad OTH

AF:

0.0382

GnomAD2 exomes

AF:

0.0510

AC:

12117

AN:

237798

AF XY:

0.0479

show subpopulations

Gnomad AFR exome

AF:

0.00784

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.0388

Gnomad EAS exome

AF:

0.000278

Gnomad FIN exome

AF:

0.0468

Gnomad NFE exome

AF:

0.0462

Gnomad OTH exome

AF:

0.0445

GnomAD4 exome

AF:

0.0456

AC:

66270

AN:

1452988

Hom.:

1854

Cov.:

AF XY:

0.0448

AC XY:

32360

AN XY:

722076

show subpopulations

African (AFR)

AF:

0.00729

AC:

243

AN:

33354

American (AMR)

AF:

0.125

AC:

5476

AN:

43828

Ashkenazi Jewish (ASJ)

AF:

0.0394

AC:

1010

AN:

25608

East Asian (EAS)

AF:

0.000734

AC:

AN:

39520

South Asian (SAS)

AF:

0.0404

AC:

3427

AN:

84766

European-Finnish (FIN)

AF:

0.0520

AC:

2714

AN:

52232

Middle Eastern (MID)

AF:

0.0201

AC:

115

AN:

5718

European-Non Finnish (NFE)

AF:

0.0457

AC:

50634

AN:

1107914

Other (OTH)

AF:

0.0437

AC:

2622

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

3389

6778

10166

13555

16944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0375

AC:

5712

AN:

152256

Hom.:

160

Cov.:

AF XY:

0.0377

AC XY:

2808

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00890

AC:

370

AN:

41554

American (AMR)

AF:

0.0792

AC:

1212

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

126

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0377

AC:

182

AN:

4822

European-Finnish (FIN)

AF:

0.0481

AC:

511

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0459

AC:

3119

AN:

67988

Other (OTH)

AF:

0.0378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

284

568

853

1137

1421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0419

Hom.:

175

Bravo

AF:

0.0396

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

E2F1-related disorder

Benign:1

Mar 06, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

20-33676727-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over