Variant 6-20490197-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001949.5(E2F3):c.1165G>A(p.Asp389Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0105 in 1,613,218 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0076 ( 8 hom., cov: 32)

Exomes 𝑓: 0.011 ( 96 hom. )

Consequence

E2F3
NM_001949.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

E2F3 (HGNC:3115): (E2F transcription factor 3) This gene encodes a member of a small family of transcription factors that function through binding of DP interaction partner proteins. The encoded protein recognizes a specific sequence motif in DNA and interacts directly with the retinoblastoma protein (pRB) to regulate the expression of genes involved in the cell cycle. Altered copy number and activity of this gene have been observed in a number of human cancers. There are pseudogenes for this gene on chromosomes 2 and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

E2F3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005552143).

BP6

Variant 6-20490197-G-A is Benign according to our data. Variant chr6-20490197-G-A is described in ClinVar as [Benign]. Clinvar id is 787663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1150 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
E2F3	NM_001949.5 linkuse as main transcript	c.1165G>A	p.Asp389Asn	missense_variant	7/7	ENST00000346618.8	NP_001940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
E2F3	ENST00000346618.8 linkuse as main transcript	c.1165G>A	p.Asp389Asn	missense_variant	7/7	1	NM_001949.5	ENSP00000262904		O00716-1
E2F3	ENST00000535432.2 linkuse as main transcript	c.772G>A	p.Asp258Asn	missense_variant	7/7	1		ENSP00000443418	P1	O00716-2

Frequencies

GnomAD3 genomes

AF:

0.00756

AC:

1150

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00727

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00912

GnomAD3 exomes

AF:

0.00729

AC:

1825

AN:

250498

Hom.:

AF XY:

0.00762

AC XY:

1032

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00705

Gnomad ASJ exome

AF:

0.00680

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00197

Gnomad FIN exome

AF:

0.00602

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00936

GnomAD4 exome

AF:

0.0108

AC:

15832

AN:

1461024

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

7773

AN XY:

726766

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00706

Gnomad4 ASJ exome

AF:

0.00699

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00202

Gnomad4 FIN exome

AF:

0.00680

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.00956

GnomAD4 genome

AF:

0.00756

AC:

1150

AN:

152194

Hom.:

Cov.:

AF XY:

0.00707

AC XY:

526

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.00727

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00902

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00729

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.00716

AC:

869

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0124

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	E2F3: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.099

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.94

L;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.010

N;N

REVEL

Benign

0.086

Sift

Benign

0.27

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.017

B;.

Vest4

0.20

MVP

0.44

MPC

0.26

ClinPred

0.027

GERP RS

5.5

Varity_R

0.049

gMVP

0.27

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