Genetic Variant E2F7:c.1124-129G>A (chr12-77034171-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_203394.3(E2F7):c.1124-129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 714,984 control chromosomes in the GnomAD database, including 65,853 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 0.38 ( 12037 hom., cov: 32)

Exomes 𝑓: 0.43 ( 53816 hom. )

Consequence

E2F7
NM_203394.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.204

Publications

8 publications found

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:

ENSG00000294230 (HGNC:):

ENSG00000294230 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F7	NM_203394.3	MANE Select	c.1124-129G>A		intron	N/A	NP_976328.2	Q96AV8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
E2F7	ENST00000322886.12	TSL:1 MANE Select	c.1124-129G>A	intron	N/A	ENSP00000323246.7	Q96AV8-1
E2F7	ENST00000550669.5	TSL:1	c.1124-129G>A	intron	N/A	ENSP00000448245.1	F8VSE7
E2F7	ENST00000919447.1		c.1124-168G>A	intron	N/A	ENSP00000589506.1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58365

AN:

151852

Hom.:

12027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.355

GnomAD4 exome

AF:

0.432

AC:

243144

AN:

563014

Hom.:

53816

AF XY:

0.431

AC XY:

122093

AN XY:

283242

show subpopulations

African (AFR)

AF:

0.231

AC:

2966

AN:

12848

American (AMR)

AF:

0.449

AC:

4646

AN:

10346

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

4253

AN:

12498

East Asian (EAS)

AF:

0.320

AC:

8381

AN:

26226

South Asian (SAS)

AF:

0.371

AC:

9407

AN:

25386

European-Finnish (FIN)

AF:

0.489

AC:

13621

AN:

27872

Middle Eastern (MID)

AF:

0.311

AC:

676

AN:

2172

European-Non Finnish (NFE)

AF:

0.450

AC:

188031

AN:

417818

Other (OTH)

AF:

0.401

AC:

11163

AN:

27848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6939

13878

20816

27755

34694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4344

8688

13032

17376

21720

<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:

0.384

AC:

58404

AN:

151970

Hom.:

12037

Cov.:

AF XY:

0.386

AC XY:

28660

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.233

AC:

9657

AN:

41446

American (AMR)

AF:

0.454

AC:

6929

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

1139

AN:

3468

East Asian (EAS)

AF:

0.302

AC:

1561

AN:

5174

South Asian (SAS)

AF:

0.391

AC:

1882

AN:

4816

European-Finnish (FIN)

AF:

0.477

AC:

5025

AN:

10524

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.457

AC:

31037

AN:

67956

Other (OTH)

AF:

0.351

AC:

742

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1779

3557

5336

7114

8893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.414

Hom.:

6884

Bravo

AF:

0.373

Asia WGS

AF:

0.338

AC:

1174

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

-0.20

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over