Variant chr16-2235356-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004424.5(E4F1):c.2139C>T(p.Ile713Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,609,234 control chromosomes in the GnomAD database, including 134,148 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 0.33 ( 9773 hom., cov: 33)

Exomes 𝑓: 0.41 ( 124375 hom. )

Consequence

E4F1
NM_004424.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

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]

E4F1 links:

E4F1 (HGNC:):

E4F1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=-1.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
E4F1	NM_004424.5 linkuse as main transcript	c.2139C>T	p.Ile713Ile	synonymous_variant	14/14	ENST00000301727.9	NP_004415.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
E4F1	ENST00000301727.9 linkuse as main transcript	c.2139C>T	p.Ile713Ile	synonymous_variant	14/14	1	NM_004424.5	ENSP00000301727.4		Q66K89

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49809

AN:

151970

Hom.:

9776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.330

GnomAD3 exomes

AF:

0.386

AC:

93715

AN:

242842

Hom.:

19199

AF XY:

0.396

AC XY:

52654

AN XY:

132836

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.406

Gnomad SAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.463

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.402

GnomAD4 exome

AF:

0.408

AC:

595068

AN:

1457146

Hom.:

124375

Cov.:

AF XY:

0.411

AC XY:

298254

AN XY:

725006

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.294

Gnomad4 ASJ exome

AF:

0.346

Gnomad4 EAS exome

AF:

0.419

Gnomad4 SAS exome

AF:

0.440

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.420

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.328

AC:

49819

AN:

152088

Hom.:

9773

Cov.:

AF XY:

0.331

AC XY:

24612

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.413

Gnomad4 SAS

AF:

0.436

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.426

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.382

Hom.:

11326

Bravo

AF:

0.303

Asia WGS

AF:

0.404

AC:

1399

AN:

3478

EpiCase

AF:

0.401

EpiControl

AF:

0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.0

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over