Genetic Variant NM_001949.5:c.1000-110G>A (chr6-20488003-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001949.5(E2F3):c.1000-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,484,722 control chromosomes in the GnomAD database, including 115,515 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 ( 9436 hom., cov: 33)

Exomes 𝑓: 0.39 ( 106079 hom. )

Consequence

E2F3
NM_001949.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.315

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F3	NM_001949.5 link	c.1000-110G>A		intron_variant	Intron 5 of 6	ENST00000346618.8	NP_001940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F3	ENST00000346618.8 link	c.1000-110G>A		intron_variant	Intron 5 of 6	1	NM_001949.5	ENSP00000262904.4
E2F3	ENST00000535432.2 link	c.607-110G>A		intron_variant	Intron 5 of 6	1		ENSP00000443418.1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50410

AN:

151978

Hom.:

9432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.357

GnomAD4 exome

AF:

0.392

AC:

522278

AN:

1332626

Hom.:

106079

AF XY:

0.398

AC XY:

265552

AN XY:

666590

show subpopulations

African (AFR)

AF:

0.142

AC:

4298

AN:

30272

American (AMR)

AF:

0.357

AC:

14228

AN:

39910

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

9753

AN:

23216

East Asian (EAS)

AF:

0.592

AC:

23043

AN:

38930

South Asian (SAS)

AF:

0.565

AC:

43768

AN:

77398

European-Finnish (FIN)

AF:

0.393

AC:

19146

AN:

48724

Middle Eastern (MID)

AF:

0.453

AC:

1725

AN:

3804

European-Non Finnish (NFE)

AF:

0.379

AC:

384475

AN:

1014680

Other (OTH)

AF:

0.392

AC:

21842

AN:

55692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

14906

29812

44717

59623

74529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11878

23756

35634

47512

59390

<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:

0.331

AC:

50411

AN:

152096

Hom.:

9436

Cov.:

AF XY:

0.340

AC XY:

25310

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.157

AC:

6531

AN:

41508

American (AMR)

AF:

0.350

AC:

5353

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

1512

AN:

3472

East Asian (EAS)

AF:

0.590

AC:

3045

AN:

5164

South Asian (SAS)

AF:

0.577

AC:

2775

AN:

4812

European-Finnish (FIN)

AF:

0.395

AC:

4167

AN:

10556

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.379

AC:

25787

AN:

67970

Other (OTH)

AF:

0.356

AC:

753

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1660

3320

4979

6639

8299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.376

Hom.:

20130

Bravo

AF:

0.317

Asia WGS

AF:

0.506

AC:

1761

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.4

(source)

DANN

Benign

0.57

PhyloP100

0.32

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over