Variant chr12-77024180-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_203394.3(E2F7):c.2571A>C(p.Pro857=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,610,532 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

E2F7
NM_203394.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0240

Variant links:

Genes affected

E2F7 (HGNC:23820): (E2F transcription factor 7) Enables DNA-binding transcription factor activity; cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in several processes, including DNA damage response, signal transduction by p53 class mediator; regulation of transcription, DNA-templated; and sprouting angiogenesis. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

E2F7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009202778).

BP6

Variant 12-77024180-T-G is Benign according to our data. Variant chr12-77024180-T-G is described in ClinVar as [Benign]. Clinvar id is 707899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.024 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
E2F7	NM_203394.3 linkuse as main transcript	c.2571A>C	p.Pro857=	synonymous_variant	13/13	ENST00000322886.12	NP_976328.2
E2F7	XM_011537966.3 linkuse as main transcript	c.2436A>C	p.Pro812=	synonymous_variant	12/12		XP_011536268.1
E2F7	XM_011537969.3 linkuse as main transcript	c.2268A>C	p.Pro756=	synonymous_variant	12/12		XP_011536271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
E2F7	ENST00000322886.12 linkuse as main transcript	c.2571A>C	p.Pro857=	synonymous_variant	13/13	1	NM_203394.3	ENSP00000323246	P1	Q96AV8-1
E2F7	ENST00000416496.6 linkuse as main transcript	c.2146A>C	p.Ser716Arg	missense_variant	12/12	5		ENSP00000393639		Q96AV8-2

Frequencies

GnomAD3 genomes

AF:

0.00100

AC:

152

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000272

AC:

AN:

246056

Hom.:

AF XY:

0.000248

AC XY:

AN XY:

133222

show subpopulations

Gnomad AFR exome

AF:

0.00341

Gnomad AMR exome

AF:

0.000241

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000671

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.000117

AC:

171

AN:

1458434

Hom.:

Cov.:

AF XY:

0.0000923

AC XY:

AN XY:

725632

show subpopulations

Gnomad4 AFR exome

AF:

0.00393

Gnomad4 AMR exome

AF:

0.000321

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000700

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.00101

AC:

153

AN:

152098

Hom.:

Cov.:

AF XY:

0.000874

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00330

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000629

Hom.:

Bravo

AF:

0.00131

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

2.1

DANN

Uncertain

1.0

Eigen

Benign

0.059

Eigen_PC

Benign

-0.0035

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.36

M_CAP

Benign

0.012

MetaRNN

Benign

0.0092

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N

PROVEAN

Benign

-0.63

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

0.96

Vest4

0.23

MutPred

0.24

Gain of catalytic residue at S716 (P = 0.001);

MVP

0.39

ClinPred

0.030

GERP RS

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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