Genetic Variant E2F1:c.*914C>G (chr20-33675818-G-C) – 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.*914C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 185,128 control chromosomes in the GnomAD database, including 967 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 0.080 ( 749 hom., cov: 32)

Exomes 𝑓: 0.10 ( 218 hom. )

Consequence

E2F1
NM_005225.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.348

Publications

23 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F1	NM_005225.3 link	c.*914C>G		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.*914C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_005225.3	ENSP00000345571.5		Q01094

Frequencies

GnomAD3 genomes

AF:

0.0802

AC:

12190

AN:

152046

Hom.:

749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.0795

Gnomad ASJ

AF:

0.0749

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0970

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0930

Gnomad OTH

AF:

0.0541

GnomAD4 exome

AF:

0.102

AC:

3364

AN:

32964

Hom.:

218

Cov.:

AF XY:

0.101

AC XY:

1734

AN XY:

17220

show subpopulations

African (AFR)

AF:

0.0191

AC:

AN:

734

American (AMR)

AF:

0.0470

AC:

AN:

702

Ashkenazi Jewish (ASJ)

AF:

0.0784

AC:

AN:

1084

East Asian (EAS)

AF:

0.273

AC:

867

AN:

3180

South Asian (SAS)

AF:

0.120

AC:

AN:

274

European-Finnish (FIN)

AF:

0.0799

AC:

325

AN:

4070

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.0875

AC:

1827

AN:

20880

Other (OTH)

AF:

0.0919

AC:

172

AN:

1872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

144

288

432

576

720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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

AF:

0.0801

AC:

12187

AN:

152164

Hom.:

749

Cov.:

AF XY:

0.0819

AC XY:

6090

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0229

AC:

951

AN:

41534

American (AMR)

AF:

0.0795

AC:

1216

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0749

AC:

260

AN:

3472

East Asian (EAS)

AF:

0.317

AC:

1628

AN:

5142

South Asian (SAS)

AF:

0.128

AC:

618

AN:

4824

European-Finnish (FIN)

AF:

0.0970

AC:

1027

AN:

10592

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0930

AC:

6324

AN:

67986

Other (OTH)

AF:

0.0536

AC:

113

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

558

1117

1675

2234

2792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0439

Hom.:

Bravo

AF:

0.0757

Asia WGS

AF:

0.185

AC:

642

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

8.9

(source)

DANN

Benign

0.49

PhyloP100

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over