Variant 6-20402579-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000346618.8(E2F3):c.347C>T(p.Pro116Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,497,894 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 8 hom. )

Consequence

E2F3
ENST00000346618.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.765

Variant links:

Genes affected

LOC124901482 (HGNC:):

LOC124901482 links:

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004159391).

BP6

Variant 6-20402579-C-T is Benign according to our data. Variant chr6-20402579-C-T is described in ClinVar as [Benign]. Clinvar id is 708917.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00628 (955/152094) while in subpopulation AFR AF= 0.0214 (889/41536). AF 95% confidence interval is 0.0202. There are 10 homozygotes in gnomad4. There are 455 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 955 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901482	XM_047419652.1 linkuse as main transcript	c.194G>A	p.Trp65Ter	stop_gained	1/3		XP_047275608.1
E2F3	NM_001949.5 linkuse as main transcript	c.347C>T	p.Pro116Leu	missense_variant	1/7	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.347C>T	p.Pro116Leu	missense_variant	1/7	1	NM_001949.5	ENSP00000262904		O00716-1

Frequencies

GnomAD3 genomes

AF:

0.00629

AC:

956

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00126

AC:

139

AN:

110410

Hom.:

AF XY:

0.000901

AC XY:

AN XY:

65498

show subpopulations

Gnomad AFR exome

AF:

0.0237

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000753

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000586

AC:

789

AN:

1345800

Hom.:

Cov.:

AF XY:

0.000505

AC XY:

337

AN XY:

667456

show subpopulations

Gnomad4 AFR exome

AF:

0.0200

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000935

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000851

Gnomad4 OTH exome

AF:

0.00163

GnomAD4 genome

AF:

0.00628

AC:

955

AN:

152094

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

455

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000187

Hom.:

Bravo

AF:

0.00763

ExAC

AF:

0.00158

AC:

171

Asia WGS

AF:

0.00116

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.23

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.74

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.14

REVEL

Benign

0.042

Sift

Benign

0.39

Sift4G

Benign

0.38

Polyphen

0.0030

Vest4

0.26

MVP

0.18

MPC

0.67

ClinPred

0.016

GERP RS

2.2

Varity_R

0.044

gMVP

0.28

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