rs3213182

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_005225.3(E2F1):c.*1305T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0723 (AC=11,752) in the gnomAD database across 162,480 control chromosomes, including 608 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.108. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.072 ( 570 hom., cov: 32)

Exomes 𝑓: 0.078 ( 38 hom. )

Consequence

E2F1
NM_005225.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.229

Publications

15 publications found

Variant links:

Genes affected

E2F1 (HGNC:3113): (E2F transcription factor 1) The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis. [provided by RefSeq, Jul 2008]

E2F1 links:

NECAB3 (HGNC:15851): (N-terminal EF-hand calcium binding protein 3) The protein encoded by this gene interacts with the amino-terminal domain of the neuron-specific X11-like protein (X11L), inhibits the association of X11L with amyloid precursor protein through a non-competitive mechanism, and abolishes the suppression of beta-amyloid production by X11L. This protein, together with X11L, may play an important role in the regulatory system of amyloid precursor protein metabolism and beta-amyloid generation. The protein is phosphorylated by NIMA-related expressed kinase 2, and localizes to the Golgi apparatus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

NECAB3 links:

ENSG00000271803 (HGNC:):

ENSG00000271803 links:

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new If you want to explore the variant's impact on the transcript NM_005225.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.1080 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_005225.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F1	NM_005225.3	MANE Select	c.*1305T>G		downstream_gene	N/A	NP_005216.1	Q01094

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F1	ENST00000343380.6	TSL:1 MANE Select	c.*1305T>G		downstream_gene	N/A	ENSP00000345571.5	Q01094
	ENSG00000271803	ENST00000606866.1	TSL:3	n.*47A>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0720

AC:

10942

AN:

152010

Hom.:

570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.0624

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.0420

Gnomad FIN

AF:

0.0625

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0871

GnomAD4 exome

AF:

0.0782

AC:

810

AN:

10352

Hom.:

Cov.:

AF XY:

0.0805

AC XY:

440

AN XY:

5464

show subpopulations

African (AFR)

AF:

0.0170

AC:

AN:

236

American (AMR)

AF:

0.0340

AC:

AN:

206

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

AN:

334

East Asian (EAS)

AF:

0.00

AC:

AN:

1194

South Asian (SAS)

AF:

0.0303

AC:

AN:

European-Finnish (FIN)

AF:

0.0601

AC:

AN:

1264

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0953

AC:

612

AN:

6424

Other (OTH)

AF:

0.0927

AC:

AN:

572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0719

AC:

10942

AN:

152128

Hom.:

570

Cov.:

AF XY:

0.0691

AC XY:

5137

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0182

AC:

758

AN:

41522

American (AMR)

AF:

0.0624

AC:

953

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

525

AN:

3468

East Asian (EAS)

AF:

0.000198

AC:

AN:

5148

South Asian (SAS)

AF:

0.0424

AC:

205

AN:

4832

European-Finnish (FIN)

AF:

0.0625

AC:

662

AN:

10592

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7481

AN:

67980

Other (OTH)

AF:

0.0871

AC:

183

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

514

1028

1542

2056

2570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0924

Hom.:

882

Bravo

AF:

0.0712

Asia WGS

AF:

0.0270

AC:

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0000830

AC:

AN:

120966

Turkish Variome

AF:

0.116

AC:

179

AN:

1542

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.000223

AC:

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.0798

AC:

187

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.7

(source)

DANN

Benign

0.58

PhyloP100

0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over