Variant rs3213177 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. Variant has been reported in ClinVar as Benign (★).

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 criteria provided, single submitter B:1

Conservation

PhyloP100: 0.881

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 20-33676727-C-A is Benign according to our data. Variant chr20-33676727-C-A is described in ClinVar as [Benign]. Clinvar id is 3055516.Status of the report is criteria_provided_single_submitter, 1 stars.

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/exons	MANE	UniProt
E2F1	NM_005225.3 linkuse as main transcript	c.*5G>T		3_prime_UTR_variant	7/7	ENST00000343380.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
E2F1	ENST00000343380.6 linkuse as main transcript	c.*5G>T		3_prime_UTR_variant	7/7	1	NM_005225.3	P1

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

GnomAD3 exomes

AF:

0.0510

AC:

12117

AN:

237798

Hom.:

513

AF XY:

0.0479

AC XY:

6184

AN XY:

129198

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 SAS exome

AF:

0.0387

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

Gnomad4 AFR exome

AF:

0.00729

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.0394

Gnomad4 EAS exome

AF:

0.000734

Gnomad4 SAS exome

AF:

0.0404

Gnomad4 FIN exome

AF:

0.0520

Gnomad4 NFE exome

AF:

0.0457

Gnomad4 OTH exome

AF:

0.0437

GnomAD4 genome

AF:

0.0375

AC:

5712

AN:

152256

Hom.:

160

Cov.:

AF XY:

0.0377

AC XY:

2808

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00890

Gnomad4 AMR

AF:

0.0792

Gnomad4 ASJ

AF:

0.0363

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0377

Gnomad4 FIN

AF:

0.0481

Gnomad4 NFE

AF:

0.0459

Gnomad4 OTH

AF:

0.0378

Alfa

AF:

0.0402

Hom.:

Bravo

AF:

0.0396

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

E2F1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 2019

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

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over